Identification of Potential Biomarkers for Major Depressive Disorder: Based on Integrated Bioinformatics and Clinical Validation.

Major depressive disorder (MDD) is a severe mental illness characterized by a lack of objective biomarkers. Mounting evidence suggests there are extensive transcriptional molecular changes in the prefrontal cortex (PFC) of individuals with MDD. However, it remains unclear whether there are specific genes that are consistently altered and possess diagnostic power. In this study, we conducted a systematic search of PFC datasets of MDD patients from the Gene Expression Omnibus database. We calculated the differential expression of genes (DEGs) and identified robust DEGs using the RRA and MetaDE methods. Furthermore, we validated the consistently altered genes and assessed their diagnostic power through enzyme-linked immunosorbent assay experiments in our clinical blood cohort. Additionally, we evaluated the diagnostic power of hub DEGs in independent public blood datasets. We obtained eight PFC datasets, comprising 158 MDD patients and 263 healthy controls, and identified a total of 1468 unique DEGs. Through integrated analysis, we identified 290 robustly altered DEGs. Among these, seven hub DEGs (SLC1A3, PON2, AQP1, EFEMP1, GJA1, CENPD, HSD11B1) were significantly down-regulated at the protein level in our clinical blood cohort. Moreover, these hub DEGs exhibited a negative correlation with the Hamilton Depression Scale score (P < 0.05). Furthermore, these hub DEGs formed a panel with promising diagnostic power in three independent public blood datasets (average AUCs of 0.85) and our clinical blood cohort (AUC of 0.92). The biomarker panel composed of these genes demonstrated promising diagnostic efficacy for MDD and serves as a useful tool for its diagnosis.

Robust and Superhydrophobic Polydimethylsiloxane/Ni@Ti3C2Tx Nanocomposite Coatings with Assembled Eyelash-Like Microstructure Array: A New Approach for Effective Passive Anti-Icing and Active Photothermal Deicing.

To solve the problem of ice condensation and adhesion, it is urgent to develop new anti-icing and deicing technologies. This study presented the development of a highly efficient photothermal-enhanced superhydrophobic PDMS/Ni@Ti3C2Tx composite film (m-NMPA) fabricated cost-effectively and straightforwardly. This film was fabricated utilizing PDMS as a hydrophobic agent, adhesive, and surface protector, while Ni@Ti3C2Tx as a magnetic photothermal filler innovatively. Through a simple spraying method, the filler is guided by a strong magnetic field to self-assemble into an eyelash-like microstructure array. The unique structure not only imparts superhydrophobic properties to the surface but also constructs an efficient "light-capturing" architecture. Remarkably, the m-NMPA film demonstrates outstanding superhydrophobic passive anti-icing and efficient photothermal active deicing performance without the use of fluorinated chemicals. The micro-/nanostructure of the film forms a gas layer, significantly delaying the freezing time of water. Particularly under extreme cold conditions (-30 °C), the freezing time is extended by a factor of 7.3 compared to the bare substrate. Furthermore, under sunlight exposure, surface droplets do not freeze. The excellent photothermal performance is attributed to the firm anchoring of nickel particles on the MXene surface, facilitating effective "point-to-face" photothermal synergy. The eyelash-like microarray structure enhances light-capturing capability, resulting in a high light absorption rate of 98%. Furthermore, the microstructure aids in maintaining heat at the uppermost layer of the surface, maximizing the utilization of thermal energy for ice melting and frost thawing. Under solar irradiation, the m-NMPA film can rapidly melt approximately a 4 mm thick ice layer within 558 s and expel the melted water promptly, reducing the risk of secondary icing. Additionally, the ice adhesion force on the surface of the m-NMPA film is remarkably low, with an adhesion strength of approximately 4.7 kPa for a 1 × 1 cm2 ice column. After undergoing rigorous durability tests, including xenon lamp weathering test, pressure resistance test, repeated adhesive tape testing, xenon lamp irradiation, water drop impact testing, and repeated brushing with hydrochloric acid and particles, the film's surface structure and superhydrophobic performance have remained exceptional. The photothermal superhydrophobic passive anti-icing and active deicing technology in this work rely on sustainable solar energy for efficient heat generation. It presents broad prospects for practical applications with advantages such as simple processing method, environmental friendliness, outstanding anti-icing effects, and exceptional durability.

Synthesis of ß,ß-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

Macrophage MCT4 inhibition activates reparative genes and protects from atherosclerosis by histone H3 lysine 18 lactylation.

Macrophage activation is a hallmark of atherosclerosis, accompanied by a switch in core metabolism from oxidative phosphorylation to glycolysis. The crosstalk between metabolic rewiring and histone modifications in macrophages is worthy of further investigation. Here, we find that lactate efflux-associated monocarboxylate transporter 4 (MCT4)-mediated histone lactylation is closely related to atherosclerosis. Histone H3 lysine 18 lactylation dependent on MCT4 deficiency activated the transcription of anti-inflammatory genes and tricarboxylic acid cycle genes, resulting in the initiation of local repair and homeostasis. Strikingly, histone lactylation is characteristically involved in the stage-specific local repair process during M1 to M2 transformation, whereas histone methylation and acetylation are not. Gene manipulation and protein hydrolysis-targeted chimerism technology are used to confirm that MCT4 deficiency favors ameliorating atherosclerosis. Therefore, our study shows that macrophage MCT4 deficiency, which links metabolic rewiring and histone modifications, plays a key role in training macrophages to become repair and homeostasis phenotypes.

Unbiased metastatic niche-labeling identifies estrogen receptor-positive macrophages as a barrier of T cell infiltration during bone colonization.

Microenvironment niches determine cellular fates of metastatic cancer cells. However, robust and unbiased approaches to identify niche components and their molecular profiles are lacking. We established Sortase A-Based Microenvironment Niche Tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastatic colonization. SAMENT was applied to multiple cancer models colonizing the same organ and the same cancer to different organs. Common metastatic niche features include macrophage enrichment and T cell depletion. Macrophage niches are phenotypically diverse between different organs. In bone, macrophages express the estrogen receptor alpha (ERα) and exhibit active ERα signaling in male and female hosts. Conditional knockout of Esr1 in macrophages significantly retarded bone colonization by allowing T cell infiltration. ERα expression was also discovered in human bone metastases of both genders. Collectively, we identified a unique population of ERα+ macrophages in the metastatic niche and functionally tied ERα signaling in macrophages to T cell exclusion during metastatic colonization. HIGHLIGHTS: SAMENT is a robust metastatic niche-labeling approach amenable to single-cell omics.Metastatic niches are typically enriched with macrophages and depleted of T cells.Direct interaction with cancer cells induces ERα expression in niche macrophages. Knockout of Esr1 in macrophages allows T cell infiltration and retards bone colonization.

Clinical efficacy of Zhiyang Xiaozhen granules combined with second-generation antihistamine in the treatment of chronic urticaria. / 止痒消疹颗粒联合第2ä»£æŠ—ç»„èƒºè¯æ²»ç–—æ ¢æ€§è¨éº»ç–¹çš„ä¸´åºŠç–—æ•ˆ.

OBJECTIVES: Chronic urticaria presents a chronic process of recurrent attacks, and its first-line treatment is second-generation antihistamine with limited treatment options. The efficacy of antihistamine varies among individuals and cannot meet the needs of all patients. This study aims to explore the clinical efficacy and safety of Zhiyang Xiaozhen granules combined with antihistamine in the treatment of chronic urticaria patients. METHODS: We retrospectively analyzed the clinical data of patients with chronic urticaria who visited the Xiangya Hospital of Central South University from April 2020 to March 2021. The patients who received conventional second-generation antihistamine treatment were selected as a control group, while the patients who received combined treatment with Zhiyang Xiaozhen granules on the basis of conventional second-generation antihistamine treatment were selected as an observation group. The differences in the Weekly Urticaria Activity Score (UAS7) and Dermatology Life Quality Index (DLQI) between the 2 groups before and 4 weeks after treatment were compared. The Symptom Score Reduce Index (SSRI) was used to evaluate and compare the efficacy of the 2 treatment regimens. RESULTS: After 4 weeks of treatment, the UAS7 levels in both groups were significantly reduced (P=0.001 and P<0.001, respectively). The effective rates of the control group and the observation group were 61.11% and 59.38%, respectively when converting UAS7 to SSRI for efficacy evaluation, and there was no statistically significant difference in efficacy between the 2 groups (P>0.05); however, when converting DLQI to SSRI for efficacy evaluation, the effective rates of the control group and the observation group were 33.33% and 46.88%, respectively, and the difference in efficacy between the 2 groups was statistically significant (P<0.001). There were 3 patients with adverse drug reactions related to drowsiness in both groups. CONCLUSIONS: The combination of Zhiyang Xiaozhen granules and second-generation antihistamine can effectively improve disease activity in patients with chronic urticaria, and the improvement in quality of life is better than that with the second-generation antihistamine alone.

Open-Nanogap-Induced Strong Electromagnetic Enhancement in Au/AgAu Monolayer as a Stable and Uniform SERS Substrate for Ultrasensitive Detection.

Nanogap-based plasmonic metal nanocrystals have been applied in surface-enhanced Raman scattering detection, while the closed and insufficient electromagnetic fields as well as the nonreproducible Raman signal of the substrate greatly restrict the actual application. Herein, a highly uniform Au/AgAu monolayer with abundant nanogaps and huge electromagnetic enhancement is prepared, which shows ultrasensitive and reproducible SERS detection. Au/AgAu with an inner nanogap is first prepared based on Au nanotriangles, and the nanogap is opened from the three tips via a subsequent etching process. The open-gap Au/AgAu displays much higher SERS efficiency than Au and Au/AgAu with an inner nanogap on detecting crystal violet due to the open-gap induced electromagnetic enhancement and improved molecular absorption. Furthermore, the open-gap Au/AgAu monolayer is prepared via interfacial self-assembly, which shows further improved SERS due to the dense and strong hotspots in the nanocavities induced by the electromagnetic coupling between adjacent open gaps. The monolayer possesses excellent signal stability, uniformity, and reproducibility. The analytic enhancement factor and relative standard deviation reach to 2.12 × 108 and 4.65% on detecting crystal violet, respectively. Moreover, the monolayer achieves efficient detection of thiram in apple juice, biphenyl-4-thiol, 4-mercaptobenzoic, melamine, and a mixed solution of four different molecules, showing great promise in practical detection.

Ambient air pollution, lifestyle, and genetic predisposition on all-cause and cause-specific mortality: A prospective cohort study.

BACKGROUND: Although it is widely acknowledged that long-term exposure to ambient air pollution is closely related to the risk of mortality, there were inconsistencies in terms of cause-specific mortality and it is still unknown whether lifestyle and genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study involved 461,112 participants from the UK Biobank. The land-use regression model was used to estimate the concentrations of particulate matter (PM2.5, PMcoarse, PM10), and nitrogen oxides (NO2 and NOx). The association between air pollution and mortality was evaluated using Cox proportional hazard models. Furthermore, a lifestyle score incorporated with smoking status, physical activity, alcohol consumption, and diet behaviors, and polygenic risk score using 12 genetic variants, were developed to assess the modifying effect of air pollution on mortality outcomes. RESULTS: During a median follow-up of 14.0 years, 33,903 deaths were recorded, including 17,083 (2835; 14,248), 6970, 2429, and 1287 deaths due to cancer (lung cancer, non-lung cancer), cardiovascular disease (CVD), respiratory and digestive disease, respectively. Each interquartile range (IQR) increase in PM2.5, NO2 and NOx was associated with 7 %, 6 % and 5 % higher risk of all-cause mortality, respectively. Specifically, for cause-specific mortality, each IQR increase in PM2.5, NO2 and NOx was also linked to mortality due to cancer (lung cancer and non-lung cancer), CVD, respiratory and digestive disease. Furthermore, additive and multiplicative interactions were identified between high ambient air pollution and unhealthy lifestyle on mortality. In addition, associations between air pollution and mortality were modified by lifestyle behaviors. CONCLUSION: Long-term exposure to air pollutants increased the risk of all-cause and cause-specific mortality, which was modified by lifestyle behaviors. In addition, we also revealed a synergistically detrimental effect between air pollution and an unhealthy lifestyle, suggesting the significance of joint air pollution management and adherence to a healthy lifestyle on public health.

Corrigendum: Association between napping and type 2 diabetes mellitus.

[This corrects the article DOI: 10.3389/fendo.2024.1294638.].

Role and mechanism of NCAPD3 in promoting malignant behaviors in gastric cancer.

Background: Gastric cancer (GC) is one of the major malignancies threatening human lives and health. Non-SMC condensin II complex subunit D3 (NCAPD3) plays a crucial role in the occurrence of many diseases. However, its role in GC remains unexplored. Materials and Methods: The Cancer Genome Atlas (TCGA) database, clinical samples, and cell lines were used to analyze NCAPD3 expression in GC. NCAPD3 was overexpressed and inhibited by lentiviral vectors and the CRISPR/Cas9 system, respectively. The biological functions of NCAPD3 were investigated in vitro and in vivo. Gene microarray, Gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms. Results: NCAPD3 was highly expressed in GC and was associated with a poor prognosis. NCAPD3 upregulation significantly promoted the malignant biological behaviors of gastric cancer cell, while NCAPD3 inhibition exerted a opposite effect. NCAPD3 loss can directly inhibit CCND1 and ESR1 expression to downregulate the expression of downstream targets CDK6 and IRS1 and inhibit the proliferation of gastric cancer cells. Moreover, NCAPD3 loss activates IRF7 and DDIT3 to regulate apoptosis in gastric cancer cells. Conclusion: Our study revealed that NCAPD3 silencing attenuates malignant phenotypes of GC and that it is a potential target for GC treatment.

The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression.

Circadian clock perturbation frequently occurs in cancer and facilitates tumor progression by regulating malignant growth and shaping the immune microenvironment. Emerging evidence has indicated that clock genes are disrupted in melanoma and linked to immune escape. Here, we found that the expression of retinoic acid receptor-related orphan receptor-α (RORA) is downregulated in melanoma patients and that patients with higher RORA expression have a better prognosis after immunotherapy. Additionally, RORA was significantly positively correlated with T-cell infiltration and recruitment. Overexpression or activation of RORA stimulated cytotoxic T-cell-mediated antitumor responses. RORA bound to the CD274 promoter and formed an inhibitory complex with HDAC3 to suppress PD-L1 expression. In contrast, the DEAD-box helicase family member DDX3X competed with HDAC3 for binding to RORA, and DDX3X overexpression promoted RORA release from the suppressive complex and thereby increased PD-L1 expression to generate an inhibitory immune environment. The combination of a RORA agonist with an anti-CTLA4 antibody synergistically increased T-cell antitumor immunity in vivo. A score based on the combined expression of HDAC3, DDX3X and RORA correlated with immunotherapy response in melanoma patients. Together, this study elucidates a mechanism of clock component-regulated antitumor immunity, which will help inform the use of immunotherapy and lead to improved outcomes for melanoma patients receiving combined therapeutic treatments.

TiN/anatase/rutile phase junction obtained by in-situ thermal transformation for efficient photothermal-assisted photocatalytic hydrogen generation.

Phase junctions exhibit great potential in photocatalytic energy conversion, yet the narrow light response region and inefficient charge transfer limit their photocatalytic performance. Herein, an anatase/rutile phase junction modified by plasmonic TiN and oxygen vacancies (TiN/(A-R-TiO2-Ov)) is prepared through an in-situ thermal transformation from TiN for efficient photothermal-assisted photocatalytic hydrogen production for the first time. The content of TiN, oxygen vacancies, and phase components in TiN/(A-R-TiO2-Ov) hybrids can be well-adjusted by tuning the heating time. The as-prepared photocatalysts display a large specific area and wide light absorption due to the synergistic effect of plasmonic excitation, oxygen vacancies, and bandgap excitations. Meanwhile, the multi-interfaces between TiN, anatase, and rutile provide built-in electric fields for efficient separation of photoinduced carriers and hot electron injection via ohmic contact and type-Ⅱ band arrangement. As a result, the TiN/(A-R-TiO2-Ov) photocatalyst shows an excellent photocatalytic hydrogen generation rate of 15.07 mmol/g/h, which is 20.6 times higher than that of titanium dioxide P25. Moreover, temperature-dependent photocatalytic tests reveal that the excellent photothermal conversion caused by plasmonic heating and crystal lattice vibrations in TiN/(A-R-TiO2-Ov) has about 25 % enhancement in photocatalysis (18.84 mmol/g/h). This work provides new inspiration for developing high-performance photocatalysts by optimizing charge transfer and photothermal conversion.

Wettability behavior of DTMS modified SiO2: Experimental and molecular dynamics study.

In this research, the wetting behavior of SiO2 modified with dodecyltrimethoxysilane (DTMS) was explored using both experimental and molecular dynamics (MD) simulation approaches. The experimental results reveal that DTMS can chemically bond to the SiO2 surface, and the contact angle (CA) reaches the maximum value of 157.7° when the mass of DTMS is twice that of SiO2. The different wetting behaviors caused by DTMS grafting were analyzed by CA fitting, ionic pairs, concentration distribution, molecule orientation, and interfacial interaction energy. The results demonstrate that a 25 % DTMS grafting rate resulted in a maximum CA of 158.2°, which is ascribed to the disruption of interfacial hydrogen bonding and changes in the hydration structure caused by DTMS grafting. Moreover, the above hydrophobic SiO2 model shows a slight decrease in CA as the water temperature increases, which is consistent with the experimental findings. In contrast, an opposite change was observed for the pristine SiO2 model. Although the higher water temperature enhances the diffusion capacity of water molecules in both models, the difference in interfacial interactions is responsible for the change in CA. We hope this finding will contribute to a deeper understanding of the wetting adjustment of SiO2.

Kinetic Evaluation on Lithium Polysulfide in Weakly Solvating Electrolyte toward Practical Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.

Enhancing barley yield potential and germination rate: gene editing of HvGA20ox2 and discovery of novel allele sdw1.ZU9.

Several dwarf and semi-dwarf genes have been identified in barley. However, only a limited number have been effectively utilized in breeding programs to cultivate lodging resistant varieties. This is due to the common association of dwarf and semi-dwarf traits with negative effects on malt quality. In this study, we employed gene editing to generate three new haplotypes of sdw1/denso candidate gene gibberellin (GA) 20-oxidase2 (GA20ox2). These haplotypes induced a dwarfing phenotype and enhancing yield potential, and promoting seed dormancy, thereby reducing pre-harvest sprouting. Moreover, ß-amylase activity in the grains of the mutant lines was significantly increased, which is beneficial for malt quality. The haplotype analysis revealed significant genetic divergence of this gene during barley domestication and selection. A novel allele (sdw1.ZU9), containing a 96-bp fragment in the promoter region of HvGA20ox2, was discovered and primarily observed in East Asian and Russian barley varieties. The 96-bp fragment was associated with lower gene expression, leading to lower plant height but higher germination rate. In conclusion, HvGA20ox2 can be potentially used to develop semi-dwarf barley cultivars with high yield and improved malt quality.

Spin disorder control of topological spin texture.

Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.

MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.

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.

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.

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.