An androgen receptor-based signature to predict prognosis and identification of ORC1 as a therapeutical target for prostate adenocarcinoma.

Background: Aberrant activation of androgen receptor (AR) signaling plays a crucial role in the progression of prostate adenocarcinoma (PRAD) and contributes significantly to the development of enzalutamide resistance. In this study, we aimed to identify a novel AR-driven signature that can predict prognosis and endows potentially reveal novel therapeutic targets for PRAD. Methods: The Seurat package was used to preprocess the single-cell RNA sequencing (scRNA-seq). Differentially expressed genes were visualized using limma and pheamap packages. LASSO and multi-variate Cox regression models were established using glmnet package. The package "Consensus Cluster Plus" was utilized to perform the consensus clustering analysis. The biological roles of origin recognition complex subunit 1 (ORC1) in PRAD were determined by gain- and loss-of-function studies in vitro and in vivo. Result: We characterized the scRNA-seq data from GSE99795 and identified 10 AR-associated genes (ARGs). The ARGs model was trained and validated in internal and external cohorts. The ARGs were identified as an independent hazard factor in PRAD and correlated with clinical risk characteristics. In addition, the ARGs were found to be correlated with somatic tumor mutation burden (TMB) levels. Two groups that have distinct prognostic and molecular features were identified through consensus clustering analysis. ORC1 was identified as a critical target among these ARGs, and it ORC1 promoted proliferation and stem-like properties of PRAD cells. Chromatin immunoprecipitation (ChIP)-qPCR assay confirmed that AR could directly bind the promoter of ORC1. Activated AR/ORC1 axis contributed to enzalutamide resistance, and targeting ORC1 rendered PRAD cells more susceptible to enzalutamide. Conclusions: This study defines an AR-driven signature that AR activates ORC1 expressions to promote PRAD progression and enzalutamide resistance, which may provide novel targets for PRAD treatment.

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma.

The MYC proto-oncogenes (c-MYC, MYCN , MYCL ) are among the most deregulated oncogenic drivers in human malignancies including high-risk neuroblastoma, 50% of which are MYCN -amplified. Genetically engineered mouse models (GEMMs) based on the MYCN transgene have greatly expanded the understanding of neuroblastoma biology and are powerful tools for testing new therapies. However, a lack of c-MYC-driven GEMMs has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and therapy development given that c-MYC is also an important driver of many high-risk neuroblastomas. In this study, we report two transgenic murine neuroendocrine models driven by conditional c-MYC induction in tyrosine hydroxylase (Th) and dopamine ß-hydroxylase (Dbh)-expressing cells. c-MYC induction in Th-expressing cells leads to a preponderance of Pdx1 + somatostatinomas, a type of pancreatic neuroendocrine tumor (PNET), resembling human somatostatinoma with highly expressed gene signatures of δ cells and potassium channels. In contrast, c-MYC induction in Dbh-expressing cells leads to onset of neuroblastomas, showing a better transforming capacity than MYCN in a comparable C57BL/6 genetic background. The c-MYC murine neuroblastoma tumors recapitulate the pathologic and genetic features of human neuroblastoma, express GD2, and respond to anti-GD2 immunotherapy. This model also responds to DFMO, an FDA-approved inhibitor targeting ODC1, which is a known MYC transcriptional target. Thus, establishing c-MYC-overexpressing GEMMs resulted in different but related tumor types depending on the targeted cell and provide useful tools for testing immunotherapies and targeted therapies for these diseases.

Alterations of the gut microbiota in patients with schizophrenia.

Introduction: Schizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect brain function via the complex gut-brain axis, which may be a potential contributor to schizophrenia. However, the alteration of gut microbiota showed high heterogeneity across different studies. Therefore, this study aims to identify the consistently altered gut microbial taxa associated with schizophrenia. Methods: We conducted a systematic search and synthesis of the up-to-date human gut microbiome studies on schizophrenia, and performed vote counting analyses to identify consistently changed microbiota. Further, we investigated the effects of potential confounders on the alteration of gut microbiota. Results: We obtained 30 available clinical studies, and found that there was no strong evidence to support significant differences in α-diversity and ß-diversity between schizophrenic patients and healthy controls. Among 428 differential gut microbial taxa collected from original studies, we found that 8 gut microbial taxa were consistently up-regulated in schizophrenic patients, including Proteobacteria, Gammaproteobacteria, Lactobacillaceae, Enterobacteriaceae, Lactobacillus, Succinivibrio, Prevotella and Acidaminococcus. While 5 taxa were consistently down-regulated in schizophrenia, including Fusicatenibacter, Faecalibacterium, Roseburia, Coprococcus and Anaerostipes. Discussion: These findings suggested that gut microbial changes in patients with schizophrenia were characterized by the depletion of anti-inflammatory butyrate-producing genera, and the enrichment of certain opportunistic bacteria genera and probiotics. This study contributes to further understanding the role of gut microbiota in schizophrenia, and developing microbiota-based diagnosis and therapy for schizophrenia.

Influence of the Original Concrete Strength and Initial Moisture Condition on the Properties Improvement of Recycled Coarse Aggregate via Accelerated Carbonation Reactions.

The physical and mechanical properties of recycled coarse aggregate (RCA) are worse than those of natural coarse aggregate (NCA), and the overall performance of recycled concrete prepared from RCA is worse than that of natural aggregate concrete. Treatment of RCA by CO2-accelerated carbonation effectively improves the macroscopic properties of RCA. The degree of influence of raw material factors, i.e., the original concrete strength (OCS) and initial moisture content (IMC) of RCA, on the carbonation of RCAs is very complex. Herein, an accelerated carbonation experiment for RCA with different material factors as variables was carried out to explore the influence of the abovementioned factors on the physical properties of carbonated recycled coarse aggregate (CRCA). By analyzing the microstructure of the RCA with the best modification effect before and after carbonation, the carbonation modification mechanism of the RCA was revealed. The physical performance indexes, including the apparent density, water absorption and carbonation rate, of the dried RCA with an OCS of C40 and C50 were significantly improved. The research results can provide basic data and theoretical support for promoting the popularization and application of RCA and recycled concrete in practical engineering.

Margin quality analysis for wedge resection of lung cancer and construction of a predictive model.

Background: Insufficient pulmonary wedge resection margin is associated with malignant positive margins and high local recurrence risk for lung cancer. This study aimed to identify the risk factors of insufficient or guideline discordant resection margin distance and establish a predictive model to preoperatively estimate the risk of discordant margin for individual patient. Methods: Guideline discordant resection margin was defined as ratio of resection margin distance to tumor size less than one. Patients who had pulmonary malignancies and underwent wedge resection between April 2014 and February 2023 were enrolled and stratified by quality of resection margin. Multivariable logistic regression analysis was employed to identify risk factors of guideline discordant margin and a predictive model was developed. Data from March 2023 to January 2024 were collected for internal validation. Results: A total of 530 patients were included. The incidence of guideline discordant wedge resection margin was 37.2%. Longer tumor's max distance to pleura and larger tumor size were variables associated with increased risk and included in the final model. Preoperative localization and right-side surgery were protective variables in the predictive model. A nomogram was built based on the predictive model. The model showed satisfying predictive performance with a concordance index of 0.720 for the predictive model, and 0.761 for internal validation. The goodness-if-fit tests were non-significant for both model development and internal validation data set. Conclusions: The preoperative predictive model and nomogram show good predictive performance to estimate the risk of guideline discordant wedge resection margin. Individualized surgical plans or preoperative nodule localization can be made for high-risk patients.

The effect of refined psychological pain nursing combined with IMB nursing on the pain, sleep and quality of life of patients after cervical cancer surgery.

To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (n = 382) and observation group (n = 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (P > .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (P < .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (P < .05). The negative emotion score of the observation group was significantly lower than that of the control group (P < .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (P < .05). The bladder function was significantly better than that of the control group (P < .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.

Mobile Colistin Resistance and Plasmid-Mediated Quinolone Resistance Genes in Escherichia coli from China, 1993-2019.

Plasmid-mediated quinolone resistance (PMQR) genes and mobile colistin resistance (MCR) genes in Escherichia coli (E. coli) have been widely identified, which is considered a global threat to public health. In the present study, we conducted an analysis of MCR genes (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5) and PMQR genes [qnrA, qnrB, qnrC, qnrD, qnrE1, qnrVC, qnrS, aac(6')-Ib-cr, qepA, and oqxAB] in E. coli from China, 1993-2019. From the 3,663 E. coli isolates examined, 1,613 (44.0%) tested positive for PMQR genes, either individually or in combination. Meanwhile, 262 isolates (7.0%) carried the MCR genes. Minimum inhibitory concentration (MIC) analyses of 17 antibiotics for the MCR gene-carrying strains revealed universal multidrug resistance. Resistance to polymyxin varied between 4 µg/mL and 64 µg/mL, with MIC50 and MIC90 at 8 µg/mL and 16 µg/mL, respectively. In addition, fluctuations in the detection rates of these resistant genes correlated with the introduction of antibiotic policies, host origin, temporal trends, and geographical distribution. Continuous surveillance of PMQR and MCR variants in bacteria is required to implement control and prevention strategies.

[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

Motor learning changes the axon initial segment of the spinal motoneuron.

We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons.

Discrete wavelet transform assisted convolutional neural network equalizer for PAM VLC system.

With the deepening of research and the further differentiation of damage types, and to compensate for both linear and nonlinear damage in visible light communication systems (VLCs), we propose a novel discrete wavelet transform-assisted convolutional neural network (DWTCNN) equalizer that combines the advantages of wavelet transform and deep learning methods. More specifically, wavelet transform is used in DWTCNN to decompose the signal into diverse coefficient series and employ an adaptive soft-threshold method to eliminate redundant information in the signal. The coefficients are then reconstructed to achieve complete signal compensation. The experimental results show that the proposed DWTCNN equalizer can significantly reduce nonlinear impairment and improve system performance with the bit error rate (BER) under the 7% hard-decision forward error correction (HD-FEC) limit of 3.8 × 10-3. We also experimentally compared DWTCNN with the Long Short-Term Memory (LSTM) and entity extraction neural network (EXNN) equalizer, the Q factor has been improved by 0.76 and 0.53 dB, and the operating ranges of the direct current (DC) bias have increased by 4.76% and 23.5%, respectively.

NFMCLDA: Predicting miRNA-based lncRNA-disease associations by network fusion and matrix completion.

In recent years, emerging evidence has revealed a strong association between dysregulations of long non-coding RNAs (lncRNAs) and sophisticated human diseases. Biological experiments are adequate to identify such associations, but they are costly and time-consuming. Therefore, developing high-quality computational methods is a challenging and urgent task in the field of bioinformatics. This paper proposes a new lncRNA-disease association inference approach NFMCLDA (Network Fusion and Matrix Completion lncRNA-Disease Association), which can effectively integrate multi-source association data. In this approach, miRNA information is used as the transition path, and an unbalanced random walk method on three-layer heterogeneous network is adopted in the preprocessing. Therefore, more effective information between networks can be mined and the sparsity problem of the association matrix can be solved. Finally, the matrix completion method accurately predicts associations. The results show that NFMCLDA can provide more accurate lncRNA-disease associations than state-of-the-art methods. The areas under the receiver operating characteristic curves are 0.9648 and 0.9713, respectively, through the cross-validation of 5-fold and 10-fold. Data from published case studies on four diseases - lung cancer, osteosarcoma, cervical cancer, and colon cancer - have confirmed the reliable predictive potential of NFMCLDA model.

High Dietary Folic Acid Supplementation Reduced the Composition of Fatty Acids and Amino Acids in Fortified Eggs.

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

Antibacterial and Anti-Inflammatory Polysaccharide from Fructus Ligustri Lucidi Incorporated in PVA/Pectin Hydrogels Accelerate Wound Healing.

In cutaneous wound healing, an overproduction of inflammatory chemokines and bacterial infections impedes the process. Hydrogels can maintain a physiologically moist microenvironment, absorb chemokines, prevent bacterial infection, inhibit bacterial reproduction, and facilitate wound healing at a wound site. The development of hydrogels provides a novel treatment strategy for the entire wound repair process. Here, a series of Fructus Ligustri Lucidi polysaccharide extracts loaded with polyvinyl alcohol (PVA) and pectin hydrogels were successfully fabricated through the freeze-thaw method. A hydrogel containing a 1% mixing weight ratio of FLL-E (named PVA-P-FLL-E1) demonstrated excellent physicochemical properties such as swellability, water retention, degradability, porosity, 00drug release, transparency, and adhesive strength. Notably, this hydrogel exhibited minimal cytotoxicity. Moreover, the crosslinked hydrogel, PVA-P-FLL-E1, displayed multifunctional attributes, including significant antibacterial properties, earlier re-epithelialization, production of few inflammatory cells, the formation of collagen fibers, deposition of collagen I, and faster remodeling of the ECM. Consequently, the PVA-P-FLL-E1 hydrogel stands out as a promising wound dressing due to its superior formulation and enhanced healing effects in wound care.

Biomimicking covalent organic frameworks nanocomposite coating for integrated enhanced anticorrosion and antifouling properties of a biodegradable magnesium stent.

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.

Integrated analysis of transcriptional changes in major depressive disorder: Insights from blood and anterior cingulate cortex.

Background: Major depressive disorder (MDD) was involved in widely transcriptional changes in central and peripheral tissues. While, previous studies focused on single tissues, making it difficult to represent systemic molecular changes throughout the body. Thus, there is an urgent need to explore the central and peripheral biomarkers with intrinsic correlation. Methods: We systematically retrieved gene expression profiles of blood and anterior cingulate cortex (ACC). 3 blood datatsets (84 MDD and 88 controls) and 6 ACC datasets (100 MDD and 100 controls) were obtained. Differential expression analysis, RobustRankAggreg (RRA) analysis, functional enrichment analysis, immune associated analysis and protein-protein interaction networks (PPI) were integrated. Furthermore, the key genes were validated in an independent ACC dataset (12 MDD and 15 controls) and a cohort with 120 MDD and 117 controls. Results: Differential expression analysis identified 2211 and 2021 differential expressed genes (DEGs) in blood and ACC, respectively. RRA identified 45 and 25 robust DEGs in blood and ACC based on DEGs, and all of them were closely associated with immune cells. Functional enrichment results showed both the robust DEGs in blood and ACC were enriched in humoral immune response. Furthermore, PPI identified 8 hub DEGs (CD79A, CD79B, CD19, MS4A1, PLP1, CLDN11, MOG, MAG) in blood and ACC. Independent ACC dataset showed the area under the curve (AUC) based on these hub DEGs was 0.77. Meanwhile, these hub DEGs were validated in the serum of MDD patients, and also showed a promising diagnostic power. Conclusions: The biomarker panel based on hub DEGs yield a promising diagnostic efficacy, and all of these hub DEGs were strongly correlated with immunity. Humoral immune response may be the key link between the brain and blood in MDD, and our results may provide further understanding for MDD.

Melatonin alleviates endoplasmic reticulum stress and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens.

Follicular atresia in chickens reduces the number of follicles that can further develop, leading to decrease egg laying. Endoplasmic reticulum stress (ERS) can initiate a unique pathway inducing the apoptosis of follicular granulosa cells, thus reducing egg laying. Melatonin (MEL) is involved in the regulation of follicle development, ovulation, and oocyte maturation, and is closely related to follicle fate. Mammalian target of Rapamycin (mTOR) signaling pathway plays an important role in cell growth regulation, and that there is a possible crosstalk between melatonin and mTOR activity in granular cells maturation and ovulation. This study aimed to investigate whether MEL inhibits ERS and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens. Frist, we established an in vitro ERS cell model using tunicamycin (TM). The results showed that different concentrations of TM exhibited dose-dependent inhibition of cell activity and induction of granulosa cells (P<0.01). Therefore, we chose 5 µg/mL of TM and a treatment time for 6 h as the optimal concentration for the following experiments. Then we investigate whether melatonin can inhibit ERS. TM treatment decreased the cell viability and Bcl-2 expression, increasing ROS levels and the mRNA expression of Grp78, ATF4, CHOP, PERK, eIF-2α, and BAX (P<0.01), whereas TM+MEL treatment significantly inhibited these changes (P<0.01). Then we explored whether melatonin protects follicular granulosa cells from ERS-induced apoptosis through the mammalian target of rapamycin (mTOR) signaling pathway by regulating ATF4, we found that ATF4 knockdown inhibited ERS by decreasing the expression of ERS-related genes and proteins and activating mTOR signaling pathway by increasing the protein expression of p4E-BP1 and pT389-S6K (P<0.001), while these changes were promoted by TM+si-ATF4+MEL treatment (P<0.01). These results indicate that MEL could alleviate TM-induced ERS by regulating ATF4 to activate mTOR signaling pathway in follicular granulosa cells, thus providing a new perspective for prolonging the laying cycle in chickens.

Multilevel design and construction in nanomembrane rolling for three-dimensional angle-sensitive photodetection.

Releasing pre-strained two-dimensional nanomembranes to assemble on-chip three-dimensional devices is crucial for upcoming advanced electronic and optoelectronic applications. However, the release process is affected by many unclear factors, hindering the transition from laboratory to industrial applications. Here, we propose a quasistatic multilevel finite element modeling to assemble three-dimensional structures from two-dimensional nanomembranes and offer verification results by various bilayer nanomembranes. Take Si/Cr nanomembrane as an example, we confirm that the three-dimensional structural formation is governed by both the minimum energy state and the geometric constraints imposed by the edges of the sacrificial layer. Large-scale, high-yield fabrication of three-dimensional structures is achieved, and two distinct three-dimensional structures are assembled from the same precursor. Six types of three-dimensional Si/Cr photodetectors are then prepared to resolve the incident angle of light with a deep neural network model, opening up possibilities for the design and manufacturing methods of More-than-Moore-era devices.

P2X7 receptor: a potential target for treating comorbid anxiety and depression.

In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5'-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.

Fluorine-18 labeling PEGylated 6-boronotryptophan for PET scanning of mice for assessing the pharmacokinetics for boron neutron capture therapy of brain tumors.

Two tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies. Shorter PEG compound 6-boronotryptophanPEG200[18F] was obtained in 1.7 % radiochemical yield and the PET-derived radioradioactivity percentage in 18 % was taken up by U87 tumor at the limb of xenograft mouse. As high as tumor to normal uptake ratio in 170 (T/N) was obtained while an inferior radioactivity uptake of 3 % and T/N of 8 was observed in LN229 xenografted mouse.