A giant planet candidate transiting a white dwarf.

Astronomers have discovered thousands of planets outside the Solar System1, most of which orbit stars that will eventually evolve into red giants and then into white dwarfs. During the red giant phase, any close-orbiting planets will be engulfed by the star2, but more distant planets can survive this phase and remain in orbit around the white dwarf3,4. Some white dwarfs show evidence for rocky material floating in their atmospheres5, in warm debris disks6-9 or orbiting very closely10-12, which has been interpreted as the debris of rocky planets that were scattered inwards and tidally disrupted13. Recently, the discovery of a gaseous debris disk with a composition similar to that of ice giant planets14 demonstrated that massive planets might also find their way into tight orbits around white dwarfs, but it is unclear whether these planets can survive the journey. So far, no intact planets have been detected in close orbits around white dwarfs. Here we report the observation of a giant planet candidate transiting the white dwarf WD 1856+534 (TIC 267574918) every 1.4 days. We observed and modelled the periodic dimming of the white dwarf caused by the planet candidate passing in front of the star in its orbit. The planet candidate is roughly the same size as Jupiter and is no more than 14 times as massive (with 95 per cent confidence). Other cases of white dwarfs with close brown dwarf or stellar companions are explained as the consequence of common-envelope evolution, wherein the original orbit is enveloped during the red giant phase and shrinks owing to friction. In this case, however, the long orbital period (compared with other white dwarfs with close brown dwarf or stellar companions) and low mass of the planet candidate make common-envelope evolution less likely. Instead, our findings for the WD 1856+534 system indicate that giant planets can be scattered into tight orbits without being tidally disrupted, motivating the search for smaller transiting planets around white dwarfs.

Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial. METHODS: Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated. RESULTS: APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice. CONCLUSION: Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.

Analysis of changes and correlation in condyle-fossa relationship after maxillary skeletal expansion.

OBJECTIVE: To investigate the changes in condyle-glenoid fossa relationship after maxillary skeletal expansion (MSE) and to verify the correlation between the condyle positional changes and expansion effect. METHODS: In this study, 20 patients (mean age 21.1 ± 5.7 years, 8 male, 12 female) with maxillary transverse deficiency (MTD) were treated with the MSE appliance, which contained molar bands and a expander with four micro-implants. The CBCT images were taken before expansion (T0), after expansion (T1) and after 6 months of maintenance (T2). The posterior TMJ space (PS), superior TMJ space (SS), anterior TMJ space, coronal lateral TMJ space (CLS), coronal medial TMJ space (CMS), condyle axis angle, maxillary basal bone width (BWM), inter-molars width, nasal bone width, molar inclination and molar palatal cusp height (U6H) were measured using Dolphin Imaging. RESULTS: At T1, compared with T0, the PS and SS significantly increased by 0.41 mm (P = .008) and 0.3 mm (P = .007). But only the SS significantly increased by 0.21 mm (P = .025) at T2. There was a significant difference of 0.37 mm (left-right, P = .014) between the left and right SS at T0, but no significant difference at T1 and T2. The increased BMW showed weak positive correlations with the change of PS (P = .015) and CMS (P = .031), and the decreased U6H showed weak negative correlations with the change of PS (P = .015) and CLS (P = .031) at T1. CONCLUSIONS: The use of MSE led to an increase in the SS and PS, which were weakly correlated with BWM and U6H. But this effect in the TMJ space gradually diminished after 6 months of maintenance, and the symmetry of the condyle-fossa relationship was preserved.

A dynamic electrically driven soft valve for control of soft hydraulic actuators.

Regulation systems for fluid-driven soft robots predominantly consist of inflexible and bulky components. These rigid structures considerably limit the adaptability and mobility of these robots. Soft valves in various forms for fluidic actuators have been developed, primarily fluidically or electrically driven. However, fluidic soft valves require external pressure sources that limit robot locomotion. State-of-the-art electrostatic valves are unable to modulate pressure beyond 3.5 kPa with a sufficient flow rate (>6 mL⋅min-1). In this work, we present an electrically powered soft valve for hydraulic actuators with mesoscale channels based on a different class of ultrahigh-power density dynamic dielectric elastomer actuators. The dynamic dielectric elastomer actuators (DEAs) are actuated at 500 Hz or above. These DEAs generate 300% higher blocked force compared with the dynamic DEAs in previous works and their loaded power density reaches 290 W⋅kg-1 at operating conditions. The soft valves are developed with compact (7 mm tall) and lightweight (0.35 g) dynamic DEAs, and they allow effective control of up to 51 kPa of pressure and a 40 mL⋅min-1 flow rate with a response time less than 0.1 s. The valves can also tune flow rates based on their driving voltages. Using the DEA soft valves, we demonstrate control of hydraulic actuators of different volumes and achieve independent control of multiple actuators powered by a single pressure source. This compact and lightweight DEA valve is capable of unprecedented electrical control of hydraulic actuators, showing the potential for future onboard motion control of soft fluid-driven robots.

CNN-HT: A Two-Stage Algorithm Selection Framework.

The No Free Lunch Theorem tells us that no algorithm can beat other algorithms on all types of problems. The algorithm selection structure is proposed to select the most suitable algorithm from a set of algorithms for an unknown optimization problem. This paper introduces an innovative algorithm selection approach called the CNN-HT, which is a two-stage algorithm selection framework. In the first stage, a Convolutional Neural Network (CNN) is employed to classify problems. In the second stage, the Hypothesis Testing (HT) technique is used to suggest the best-performing algorithm based on the statistical analysis of the performance metric of algorithms that address various problem categories. The two-stage approach can adapt to different algorithm combinations without the need to retrain the entire model, and modifications can be made in the second stage only, which is an improvement of one-stage approaches. To provide a more general structure for the classification model, we adopt Exploratory Landscape Analysis (ELA) features of the problem as input and utilize feature selection techniques to reduce the redundant ones. In problem classification, the average accuracy of classifying problems using CNN is 96%, which demonstrates the advantages of CNN compared to Random Forest and Support Vector Machines. After feature selection, the accuracy increases to 98.8%, further improving the classification performance while reducing the computational cost. This demonstrates the effectiveness of the first stage of the CNN-HT method, which provides a basis for algorithm selection. In the experiments, CNN-HT shows the advantages of the second stage algorithm as well as good performance with better average rankings in different algorithm combinations compared to the individual algorithms and another algorithm combination approach.

NDUFA4 promotes the progression of head and neck paraganglioma by inhibiting ferroptosis.

NDUFA4 is a component of respiratory chain-oxidative phosphorylation pathway. NDUFA4 is highly expressed in tumor tissues, but little is known about the function of NDUFA4 in head and neck paraganglioma (HNPGL). We examined NDUFA4 expression in tissues from 10 HNPGL patients and 6 controls using qRT-PCR and Western blotting. NDUFA4 knockdown PGL-626 cells were established by using lentivirus infection and puromycin screening. Cell viability, ATP production, lipid reactive oxygen species, and mitochondrial membrane potential assays were performed to investigate the ferroptotic effects in NDUFA4 deficiency HNPGL cancer cells. Xenograft mouse model was created to detect the synergetic antitumor action between NDUFA4 deficiency and Metformin. NDUFA4 was upregulated in tumor tissues of HNPGL patients. NDUFA4 knockdown impaired the assembly of mitochondrial respiratory chain complexes and decreased the production of ATP and reduced cancer cell viability. Mechanistically, NDUFA4 knockdown increased cell ferroptosis, which further promoted Metformin-induced ferroptosis in PGL-626 cells. Therefore, NDUFA4 deficiency enhanced Metformin-mediated inhibition of the HNPGL progression in mice. In conclusion, NDUFA4 promotes the progression of HNPGL, and NDUFA4 knockdown enhances Metformin-mediated inhibition of the HNPGL progression in a mouse model.

Infiltrating myeloid cell-derived properdin markedly promotes microglia-mediated neuroinflammation after ischemic stroke.

BACKGROUND: Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. METHODS: Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein-protein interactions, and related signaling pathways, etc. RESULTS: The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. CONCLUSION: Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.

Influence of Removing Leaf Node Neighbors on Network Controllability.

From the perspective of network attackers, finding attack sequences that can cause significant damage to network controllability is an important task, which also helps defenders improve robustness during network constructions. Therefore, developing effective attack strategies is a key aspect of research on network controllability and its robustness. In this paper, we propose a Leaf Node Neighbor-based Attack (LNNA) strategy that can effectively disrupt the controllability of undirected networks. The LNNA strategy targets the neighbors of leaf nodes, and when there are no leaf nodes in the network, the strategy attacks the neighbors of nodes with a higher degree to produce the leaf nodes. Results from simulations on synthetic and real-world networks demonstrate the effectiveness of the proposed method. In particular, our findings suggest that removing neighbors of low-degree nodes (i.e., nodes with degree 1 or 2) can significantly reduce the controllability robustness of networks. Thus, protecting such low-degree nodes and their neighbors during network construction can lead to networks with improved controllability robustness.

HDAC1 expression is positively correlated with NADPH oxidase 4-mediated oxidative stress in a mouse model of traumatic brain injury.

Accumulating evidence has demonstrated that histone deacetylase 1 (HDAC1) expression is statistically correlated with the severity of traumatic brain injury (TBI). However, the specific role of HDAC1 in the occurrence and development of TBI remains unclear. The lateral fluid percussion injury (LFPI) was used to conduct TBI mouse model in C57BL/6J and C57BL/6J-Hdac1em1cyagen mice. Western blot and qRT-PCR were performed to estimate the expression of HDAC1 and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in brain tissues. Modified neurological severity score (mNSS) and brain water content were analyzed to detect the neurological deficit. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were used to detect the oxidative stress. Oxidative stresses, HDAC1, and NOX4 expression were upregulated in the lesioned cortices tissues after TBI. HDAC1 protein expression was positively correlated with the NOX4 in TBI mouse. Hdac1 knockout attenuated brain edema and neurological dysfunction caused by TBI in mice. Hdac1 knockout inhibited the expressions of NOX4 induced by TBI and attenuated TBI-induced oxidative stress. HDAC1 expression is positively correlated with to NOX4-mediated oxidative stress in a TBI mouse model.NEW & NOTEWORTHY Traumatic brain injury causes increased oxidative stresses, histone deacetylase 1, and nicotinamide adenine dinucleotide phosphate oxidase 4 expression. Hdac1 knockout could attenuate the brain damage caused by traumatic brain injury. The results suggest that histone deacetylase 1 may be a therapeutic target for the treatment of traumatic brain injury.

miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the hippocampus and plasma of 6-month-old APPswe/PS1dE9 (APP/PS1) mice. miR-204-3p overexpression attenuated memory and synaptic deficits in APP/PS1 mice. The amyloid levels and oxidative stress were decreased in the hippocampus of APP/PS1 mice after miR-204-3p overexpression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) was a target of miR-204-3p, and Nox4 inhibition by GLX351322 protected neuronal cells against Aß1-42-induced neurotoxicity. Furthermore, GLX351322 treatment rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice. These results revealed that miR-204-3p attenuated memory deficits and oxidative stress in APP/PS1 mice by targeting Nox4, and miR-204-3p overexpression and/or Nox4 inhibition might be a potential therapeutic strategy for AD treatment.

Using machine learning models to predict HBeAg seroconversion in CHB patients receiving pegylated interferon-α monotherapy.

BACKGROUND AND OBJECTIVE: Though there are many advantages of pegylated interferon-α (PegIFN-α) treatment to chronic hepatitis B (CHB) patients, the response rate of PegIFN-α is only 30 ~ 40%. Therefore, it is important to explore predictors at baseline and establish models to improve the response rate of PegIFN-α. METHODS: We randomly divided 260 HBeAg-positive CHB patients who were not previously treated and received PegIFN-α monotherapy (180 µg/week) into a training dataset (70%) and testing dataset (30%). The intersect features were extracted from 50 routine laboratory variables using the recursive feature elimination method algorithm, Boruta algorithm, and Least Absolute Shrinkage and Selection Operator Regression algorithm in the training dataset. After that, based on the intersect features, eight machine learning models including Logistic Regression, k-Nearest Neighbors, Support Vector Machine, Decision Tree, Random Forest, Gradient Boosting, Extreme Gradient Boosting (XGBoost), and Naïve Bayes were applied to evaluate HBeAg seroconversion in HBeAg-positive CHB patients receiving PegIFN-α monotherapy in the training dataset and testing dataset. RESULTS: XGBoost model showed the best performance, which had largest AUROC (0.900, 95% CI: 0.85-0.95 and 0.910, 95% CI: 0.84-0.98, in training dataset and testing dataset, respectively), and the best calibration curve performance to predict HBeAg seroconversion. The importance of XGBoost model indicated that treatment time contributed greatest to HBeAg seroconversion, followed by HBV DNA(log), HBeAg, HBeAb, HBcAb, ALT, triglyceride, and ALP. CONCLUSIONS: XGBoost model based on common laboratory variables had good performance in predicting HBeAg seroconversion in HBeAg-positive CHB patients receiving PegIFN-α monotherapy.

2,2',4,4'-Tetrabromodiphenyl ether disrupts spermatogenesis in mice by interfering with the ER-Nrf1-Tfam-mitochondria pathway.

2,2',4,4' -tetrabromodiphenyl ether (BDE47), a well-known endocrine disruptor of the estrogen receptor (ER) is toxic to the mitochondria and spermatogenesis. This study aimed to explore the mechanism of BDE47 on spermatogenesis in mammals. Adult male Institute of Cancer Research (ICR) mice were gavaged daily with BDE47 (0, 1, or 10 mg/kg bw) for 8 weeks. Testicular weight, sperm production and motility, morphology of spermatogenic cells, nuclear respiratory factor 1 (Nrf1) level, and its expression in testes were determined. In vitro, cell viability, and key molecules in the ER-Nrf1-mitochondrial transcription factor A (Tfam)-mitochondria pathway in the immortalized mouse spermatogonia line (GC1) were determined at 48 h and 0-5 h after exposure; RNA interference (RNAi) was also performed to verify that the decreased Nrf1 was associated with mitochondrial dysfunction and the impaired viability of germ cells. The results indicated that BDE47 impaired testis weight and spermatogenesis, impaired mitochondria and germ cells, and decreased Nrf1 in the testes of mice. In vitro, after 48 h exposure, BDE47 reduced cell viability, Nrf1 protein, and mRNA of Nrf1, Tfam, ATP synthase subunit ß (Atp5b), and cytochrome c oxidase subunit I (mt-CO1) in GC1 while also reducing mRNA of Nrf1 and Tfam promptly (from 1 to 5 h) after exposure. Furthermore, Nrf1 RNA interference decreased viability and mitochondrial function in GC1. These results indicated that BDE47 disrupts spermatogenesis in mice, probably by interfering with the ER-Nrf1-Tfam-mitochondria pathway, and Nrf1 is a target molecule of BDE47 estrogen receptor.

Fiber Bragg Grating-Based Smart Garment for Monitoring Human Body Temperature.

Body temperature provides an insight into the physiological state of a person, and body temperature changes reflect much information about human health. In this study, a garment for monitoring human body temperature based on fiber Bragg grating (FBG) sensors is reported. The FBG sensor was encapsulated with a PMMA tube and calibrated in the thermostatic water bath. The results showed that FBG sensors had good vibration resistance, and the wavelength changed about 0-1 pm at a 0.5-80 Hz vibration frequency. The bending path of the optical fiber after integration with clothing is discussed. When the bending radius is equal to or greater than 20 mm, a lower bending loss can be achieved even under the bending and stretching of the human body. The FBG sensor, the optical fiber, and the garment were integrated together using hot melt glue by the electric iron and the hot press machine. Through experiments of monitoring human body temperature, the sensor can reach the human armpit temperature in about 10-15 min with the upper arm close to the torso. Because it is immune to electromagnetic interferences, the smart garment can be used in some special environments such as ultrasonography, magnetic resonance (MR), and aerospace.

N6-methyladenosine RNA modification and its interaction with regulatory non-coding RNAs in colorectal cancer.

As one of the most common forms of RNA modification, N6-methyladenosine (m6A) RNA modification has attracted increasing research interest in recent years. This reversible RNA modification added a new dimension to the post-transcriptional regulation of gene expression. In colorectal cancer (CRC), the role of m6A modification has been extensively studied, not only on mRNAs but also on non-coding RNAs (ncRNAs). In the present review, we depicted the role of m6A modification in CRC, systematically elaborate the interaction between m6A modification and regulatory ncRNAs in function and mechanism. Moreover, we discussed the potential applications in clinical.

The chromosome 19 microRNA cluster, regulated by promoter hypomethylation, is associated with tumour burden and poor prognosis in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is still one of the major malignant tumours with poor prognosis. The chromosome 19 microRNA cluster (C19MC) is the largest miRNA cluster, and its functions and regulatory mechanisms remain unclear in HCC. We extracted data from 373 HCC samples and 50 non-tumour samples from The Cancer Genome Atlas database. The differential expression levels and methylation levels of C19MC as well as the correlation between them were analysed. We evaluated the correlation between the expression levels of C19MC and the clinical features. We further performed prognostic analysis for C19MC and analysed the bioinformatic function. C19MC had upregulated expression levels and promoter hypomethylation in HCC. A significant negative correlation between the high expression and low methylation level of C19MC was obtained. In addition, the positive correlation between the expression levels of C19MC and the tumour grade, tumour stage and T-stage is shown. Three miRNAs (mir-512-1, mir-516a-1, mir-519a-2) were negatively associated with overall survival on the basis of the Kaplan-Meier analysis and the 3-miRNA signature was significant for the prognostic assessment of HCC. A bioinformatic enrichment analysis suggested that the target genes of the 3 miRNAs may be associated with mitogen-activated protein kinase pathways related to cancer invasion. In summary, our novel study demonstrated that the hypomethylation of promoters upregulates the expression levels of C19MC and that C19MC may represent a potential new candidate for the diagnosis and therapy of HCC.

Dysregulated N6-methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer.

Accumulating evidence implies that N6-methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation-relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan-Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase-like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up-trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α-smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of cutaneous melanoma.

Cutaneous malignant melanoma (hereafter called melanoma) is one of the most aggressive cancers with increasing incidence and mortality rates worldwide. In this study, we performed a systematic investigation of the tumor microenvironmental and genetic factors associated with melanoma to identify prognostic biomarkers for melanoma. We calculated the immune and stromal scores of melanoma patients from the Cancer Genome Atlas (TCGA) using the ESTIMATE algorithm and found that they were closely associated with patients' prognosis. Then the differentially expressed genes were obtained based on the immune and stromal scores, and prognostic immune-related genes further identified. Functional analysis and the protein-protein interaction network further revealed that these genes enriched in many immune-related biological processes. In addition, the abundance of six infiltrating immune cells was analyzed using prognostic immune-related genes by TIMER algorithm. The unsupervised clustering analysis using immune-cell proportions revealed eight clusters with distinct survival patterns, suggesting that dendritic cells were most abundant in the microenvironment and CD8+ T cells and neutrophils were significantly related to patients' prognosis. Finally, we validated these genes in three independent cohorts from the Gene Expression Omnibus database. In conclusion, this study comprehensively analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for melanoma.

Molecular characterization of lung cancer: A two-miRNA prognostic signature based on cancer stem-like cells related genes.

Lung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326+ and CD326- A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR-30b-5p and miR-29c-3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.

Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes.

Pregenomic RNA (pgRNA) is a direct transcription product of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and it plays important roles in viral genome amplification and replication. This study was designed to investigate whether serum pgRNA is a strong alternative marker for reflecting HBV cccDNA levels and to analyze the correlation between serum pgRNA, serum HBV DNA, and hepatitis B surface antigen (HBsAg). A total of 400 HBV-infected patients who received nucleos(t)ide analog (NA) therapy with different clinical outcomes were involved in this research. Case groups included asymptomatic hepatitis B virus carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) patients, with 100 patients in each group. The results showed that the levels of HBV pgRNA had significant differences between these 4 groups. Serum pgRNA levels correlated well with serum HBV DNA and HBsAg levels (HBV pgRNA levels versus HBV DNA levels, r = 0.58, P < 0.001; HBV pgRNA levels versus HBsAg levels, r = 0.47, P < 0.001). In addition, we focused on the 108 HBV-infected patients with HBV DNA levels of <500 IU/ml; it was surprising to find that in 17.57% (13/74) of cases, HBV pgRNA could be detected even when the HBV DNA level was below 20 IU/ml. In conclusion, HBV pgRNA levels in serum can be a surrogate marker for intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg. The detection of serum HBV pgRNA levels may provide a reference for clinical monitoring of cccDNA levels and the selection of appropriate timing for discontinuing antiviral therapy, especially when HBV DNA levels are below the detection limit.

Xingnaojing ameliorates synaptic plasticity and memory deficits in an Aß1-42 induced mouse model of Alzheimer's disease.

The accumulation of insoluble amyloid ß (Aß) peptides is one of the pathological changes in Alzheimer's disease (AD), which induced synaptic plasticity impairment and excitatory amino acid toxicity associated with decreased memory function. Xingnaojing (XNJ), a well-known prescription in traditional Chinese medicine, has been used for the treatment of stroke for many years in China. In this study, we aim to investigate the therapeutic effects of XNJ in a hippocampus of Aß1-42 induced mouse model of AD which showed significant memory loss and impaired synaptic morphology and function. Treatment of XNJ could attenuate spatial and working memory dysfunction, increase dendritic spine density and improve long-term potential (LTP) induction. In addition, XNJ treatment significantly increased the level of N-methyl-d-aspartate receptors (NMDARs) and inhibit the NMDA/α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) ratio in AD mice. XNJ treatment also activated the AKT/mechanistic target of rapamycin (mTOR) pathway, while inhibition of the mTOR pathway by rapamycin could reverse the protective effects of XNJ treatment. In conclusion, XNJ protected against synaptic plasticity and memory impairment in AD mice via the activation of AKT/mTOR signaling pathway, suggesting XNJ as an alternative treatment for AD.