Robust, in-service, and joint monitoring of a dual-polarization transceiver IQ skew for a coherent DSCM system without channel impairment compensation.

A robust, in-service, and joint monitoring of a dual-polarization (DP) transceiver IQ skew for a coherent DSCM system is proposed and experimentally validated. Unlike traditional monitoring schemes, the proposed scheme realizes robust transceiver impairments monitoring without channel impairment compensation, including chromatic dispersion (CD), polarization variation, and carrier phase noise. This enhances the stability and precision of the monitoring process and reduces computational complexity by eliminating sophisticated DSP for impairment compensation. A complex system model for a single-tone signal is given first. Based on the model, the proposed scheme enables monitoring of the DP transmitter and the receiver IQ skew using the inserted frequency domain pilots (FPTs). Experimental results show that the proposed scheme can estimate the transceiver IQ skew within 16 ps with an estimation error of less than 0.2 ps and is robust to CD, polarization variation, phase noise, and amplified spontaneous emission noise. To the best of our knowledge, the proposed scheme achieves in-service transceiver IQ skew monitoring for coherent DSCM systems for the first time.

Robust, wide-range, and precise transmitter IQ impairment monitoring scheme for coherent digital subcarrier multiplexing systems.

In this Letter, we present a robust, wide-range, and precise monitoring scheme for transmitter (Tx) impairments in coherent digital subcarrier multiplexing (DSCM) systems. The proposed scheme employs frequency-domain pilot tones (FPTs) to compensate for frequency offset (FO), polarization aliasing, and carrier phase noise, thus isolating Tx impairments from channel distortions. It then implements 4 × 4 real-valued MIMO to compensate for Tx impairments by equalizing symmetric subcarriers. Tx impairment monitoring is derived from the equalizer coefficients. By considering the phase shift caused by Tx impairments, a wide-range and precise monitoring of Tx impairments including IQ skew, IQ phase, and gain imbalances is achieved. We experimentally validated our approach using a 48-GBaud, four-subcarrier, dual-polarization coherent DSCM system. The results confirm the method's capability for a wide-range, robust, and precise Tx impairment monitoring in coherent DSCM systems, maintaining performance even in the presence of ultra-fast polarization variation.

Construction and Properties of High-Toughness Soft-Soft Interfaces Based on the Adhesion of Natural Polyphenols.

Artificial joint replacement is the most effective way to treat osteoarthritis. However, these artificial joints are too stiff with high interfacial contact stress and poor surface lubrication, resulting in stress shielding and severe wear and tear lead to an extremely high failure rate. At present, hydrogels are considered the most promising substitute for artificial joint prostheses owing to their good biocompatibility, adjustable mechanical properties, and excellent flexibility. Nevertheless, a traditional single-layer hydrogel has poor bearing capacity and lubrication, which are far from the properties of natural articular cartilage. The high strength and low friction properties of natural articular cartilage are based on its own multilayer fibrous structure. Therefore, by simulating the multilayer structure of natural cartilage, a bilayer bionic cartilage hydrogel was prepared; that is, the upper hydrogel realized excellent lubrication and the lower hydrogel realized high load-bearing capacity. However, the interface binding of bilayer hydrogels is a challenge at present. Therefore, the interfacial adhesion of the bilayer hydrogel is improved by adding tannic acid (TA) based on the adhesion of the natural polyphenol structure. The average interfacial toughness reaches 3650 J/m2, and the average interfacial shear force reaches 800 kPa. In the preparation of the bilayer hydrogel, taking advantage of the coordination reaction between TA and metal cations, Fe3+ is further added to endow the bilayer hydrogel with excellent mechanical properties and good sliding friction performance. Therefore, this work opens up a new way to construct cartilage-like materials with high toughness and a soft-soft interface.

Large-aperture single-mode 795 nm VCSEL for chip-scale nuclear magnetic resonance gyroscope with an output power of 4.1 mW at 80 °C.

Transverse optical confinement in oxide-confined vertical-cavity surface-emitting lasers (VCSELs) crucially depends on thickness of oxide layer and its position relative to a standing wave. Modifying the structure reduces the overlap between the oxide layer and the standing wave as well as effective refractive index difference between core and cladding of the VCSEL that subsequently decreases of the number of transverse modes and increases the mode extension beyond oxide aperture. A 795 nm VCSEL is designed and fabricated with this concept. The proposed device achieves high single-mode operation of 4.1 mW at 80 °C, SMSR of 41.68 dB, and OPSR of 27.4 dB. VCSEL is applied in a nuclear magnetic resonance gyroscope (NMRG) system as pump source due to its excellent device performance and satisfactory test results are obtained.

Homocysteine promotes migration of adventitial fibroblasts via angiotensin II type 1 receptor activation to aggravate atherosclerosis.

This study clarified the effect of homocysteine on adventitial fibroblasts (AFs) and its relationship with angiotensin II type 1 receptor (AT1R). Hyperhomocysteinemia aggravated the plaque area and increased the expression of IL-6, MCP-1, and macrophage infiltration in the plaque and adventitia of the aorta, whereas telmisartan improved this effect. Hyperhomocysteinemia induced the occurrence of the AFs marker protein ER-TR7 in the plaque and entire layer of the aorta, whereas telmisartan improved these effects, indicating that homocysteine induced AFs migration and that AT1R mediated this process. The migration experiments of AFs also reached the same conclusion. Homocysteine increased the phosphorylation levels of PKC and ERK1/2 in the AFs and HEK293A cells transfected with the AT1R plasmid, whereas telmisartan inhibited this effect, indicating that homocysteine activated AT1R intracellular signaling pathway. Homocysteine also increased the AFs At1R expression. Conclusion, homocysteine promoted adventitial inflammation, induced AFs migration, and aggravated atherosclerosis by activating AT1R.

SOX2 Inhibition Promotes Promoter Demethylation of CDX2 to Facilitate Gastric Intestinal Metaplasia.

BACKGROUND: Gastric intestinal metaplasia (IM) is regarded as a premalignant lesion, conferring risks for gastric cancer development. An intestinal transcription factor, CDX2, plays a vital role in establishing and maintaining IM. SOX2, an HMG-box transcription factor, is expressed in normal gastric mucosa and downregulated in IM. Therefore, it is important to elucidate the mutual interaction of SOX2 and CDX2 in gastric IM. AIMS: This study aims to evaluate the negative correlation between SOX2 and CDX2 in mRNA expression and promoter methylation and to illuminate the effect of SOX2 on the promoter methylation of CDX2. METHODS: Immunohistochemistry, real-time PCR and methylation-specific polymerase chain reaction assays were performed to evaluate the expression and promoter methylation of SOX2 and CDX2 in IM tissues from patients. SOX2 knockdown and CDX2 overexpression were performed in GES-1 cells to further clarify the relationship between SOX2 and CDX2. RESULTS: A negative correlation between SOX2 and CDX2 was found in 120 gastric IM specimens. Additionally, significant DNA demethylation of CDX2 promoter in clinical IM specimens was observed concomitantly with partial methylation of the SOX2 promoter. Furthermore, SOX2 knockdown in GES-1 cells triggered promoter demethylation of CDX2. Finally, the phenotype shift of gastric intestinal metaplasia in GES-1 cells, marked by MUC2 expression, was effectively induced by the combination of SOX2 RNAi and CDX2 overexpression. CONCLUSIONS: Aberrant DNA methylation of SOX2 and CDX2 genes contributes to the development of IM. Notably, SOX2 may play a role in establishing and maintaining the methylation status of the CDX2 gene in gastric tissues and cells.

[Blueberry anthocyanins induce G2/M cell cycle arrest and apoptosis of oral cancer KB cells through down-regulation methylation of p53].

Blueberries are an excellent source of dietary polyphenols such as anthocyanins and phenolic acids. In this study, we investigated the ability of anthocyanins from the wild blueberries of Inner Mongolia to suppress the growth of the oral cancer cell line KB. The blueberry anthocyanins were extracted with methanol-containing 0.1% (v/v) hydrochloric acid. Fourteen unique anthocyanins were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The anticancer bioactivity of the extracts on KB cells was analyzed using methylthiazolyl-tetrazolium (MTT), flow cytometry (FCM) and immunocytochemistry. It was shown that the blueberry anthocyanins suppressed the proliferation of KB cells in a dose-dependent manner, as well as induced G2/M cell cycle arrest and apoptosis of oral cancer KB cells. Immunocytochemistry analysis showed that the expression of caspase-9 and cytochrome c were obviously increased after the anthocyanins treatment. Western blot analysis also indicated that the expression of p53 was increased. Methylation-specific PCR (MSP) showed that the amount of unmethylated p53 increased, indicating that the anthocyanins can down-regulate the methylation of p53.

CFD Investigation on Combined Ventilation System for Multilayer-Caged-Laying Hen Houses.

Mechanical ventilation is an important means of environmental control in multitier laying hen cages. The mainstream ventilation mode currently in use, negative-pressure ventilation (NPV), has the drawbacks of a large temperature difference before and after adjustment and uneven air velocity distribution. To solve these problems, this study designed and analyzed a combined positive and negative-pressure ventilation system for laying hen cages. According to the principle of the conservation of mass to increase the inlet flow in the negative-pressure ventilation system on the basis of the addition of the pressure-wind body-built positive-and-negative-pressure-combined ventilation (PNCV) system, further, computational fluid dynamics (CFD) simulation was performed to analyze the distribution of environmental parameters in the chicken cage zone (CZ) with inlet angles of positive-pressure fans set at 45°, 90°, and 30°. Simulation results showed that the PNCV system increased the average air velocity in the CZ from 0.94 m/s to 1.04 m/s, 1.28 m/s, and 0.99 m/s by actively blowing air into the cage. The maximum temperature difference in the CZ with the PNCV system was 2.91 °C, 1.80 °C, and 3.78 °C, which were all lower than 4.46 °C, the maximum temperature difference in the CZ with the NPV system. Moreover, the relative humidity remained below 80% for the PNCV system and between 80% and 85% for the NPV system. Compared with the NPV system, the PNCV system increased the vertical airflow movement, causing significant cooling and dehumidifying effects. Hence, the proposed system provides an effective new ventilation mode for achieving efficient and accurate environmental control in laying hen cages.

Timing, initiation and function: An in-depth exploration of the interaction network among neutrophil extracellular traps related genes in acute pancreatitis.

BACKGROUND: Exogenous inhibition of neutrophil extracellular traps (NETs) was believed to alleviate acute pancreatitis (AP). This study aimed to comprehensively explore the key biological behavior of NETs including timing and pathogenesis in AP by integrating of single cell RNA sequencing(scRNA-seq) and bulk RNA-seq. METHODS: Differentially expressed NETs-related genes and the hub genes of NETs were screened by bulk RNA-seq. ScRNA-seq was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in neutrophils. The mouse AP models were build to verify the timing of initiation of NETs and underlying pathogenesis of damage on pancreas acinar cells. RESULTS: Tlr4 and Ccl3 were screened for hub genes by bulk RNA-seq. The trajectory analysis of neutrophils showed that high expression of Ccl3, Cybb and Padi4 can be observed in the middle stage during AP. Macrophages might be essential in the biological behavior of neutrophils and NETs. Through animal models, we presented that extensive NETs structures were formed at mid-stage of inflammation, accompanied by more serious pancreas and lung damage. NETs might promote necroptosis and macrophage infiltration in AP, and the damage on pancreatic injury could be regulated by Tlr4 pathway. Ccl3 was considered to recruit neutrophils and promote NETs formation. CONCLUSION: The findings explored the underlying timing and pathogenesis of NETs in AP for the first time, which provided gene targets for further studies.

Enhancing Energy Storage Performance of 0.85Bi0.5Na0.5TiO3-0.15LaFeO3 Lead-Free Ferroelectric Ceramics via Buried Sintering.

Bismuth sodium titanate (Bi0.5Na0.5TiO3, BNT) ceramics are expected to replace traditional lead-based materials because of their excellent ferroelectric and piezoelectric characteristics, and they are widely used in the industrial, military, and medical fields. However, BNT ceramics have a low breakdown field strength, which leads to unsatisfactory energy storage performance. In this work, 0.85Bi0.5Na0.5TiO3-0.15LaFeO3 ceramics are prepared by the traditional high-temperature solid-phase reaction method, and their energy storage performance is greatly enhanced by improving the process of buried sintering. The results show that the buried sintering method can inhibit the formation of oxygen vacancy, reduce the volatilization of Bi2O3, and greatly improve the breakdown field strength of the ceramics so that the energy storage performance can be significantly enhanced. The breakdown field strength increases from 210 kV/cm to 310 kV/cm, and the energy storage density increases from 1.759 J/cm3 to 4.923 J/cm3. In addition, the energy storage density and energy storage efficiency of these ceramics have good frequency stability and temperature stability. In this study, the excellent energy storage performance of the ceramics prepared by the buried sintering method provides an effective idea for the design of lead-free ferroelectric ceramics with high energy storage performance and greatly expands its application field.

An in-Depth Exploration of the Genetic Interaction Network Between Ferroptosis and Acute Pancreatitis.

Background: Ferroptosis plays an important role in a variety of disease processes and is equally important in pancreatic diseases. However, the role of ferroptosis-related genes (FRGs) in acute pancreatitis (AP) remains unknown, and their specific potential mechanisms still need to be explored extensively. Methods: AP-related gene microarray data were obtained from the GEO database, while FRGs were obtained from the ferroptosis database (FerrDb). Differentially expressed genes (DEGs) were screened by the "limma" package, and GSEA was performed. The corresponding ferroptosis-related differentially expressed genes (FRDEGs) were screened, and GO and KEGG pathway analyses were performed. A PPI network was constructed to identify hub FRDEGs by CytoHubba, MCODE and CTD scores. Transcription factors and miRNAs predicted using the NetworkAnalyst database were used to establish the regulatory network. Immune cell infiltration analysis was performed by the R package "ssGSEA" algorithm. The hub genes were validated by transcriptome sequencing of AP model mice and immunohistochemistry in rats and mice. Results: A total of 82 FRDEGs were screened, and these genes were mainly associated with ferroptosis, hypoxic response, autophagy, mitophagy and immune inflammation. However, we also found that these genes are also jointly involved in other cell death modalities, such as apoptosis and necroptosis. Further analysis obtained 7 hub genes from 82 genes, and single-sample gene set enrichment analysis (ssGSEA) showed that the hub genes are closely associated with the infiltration of specific immune cells and the activation of immune pathways. Conclusion: This study reveals the complex functions and important roles of ferroptosis-related genes in AP and provides gene targets for further studies of AP.

The crosstalk between ferroptosis and mitochondrial dynamic regulatory networks.

Ferroptosis is an iron-driven cell death modality characterized by iron accumulation and excessive lipid peroxidation. Ferroptosis is closely related to mitochondrial function, as indicated by studies showing that mitochondrial dysfunction and damage promote oxidative stress, which in turn induces ferroptosis. Mitochondria play crucial roles in cellular homeostasis, and abnormalities in their morphology and function are closely associated with the development of many diseases. Mitochondria are highly dynamic organelles, and their stability is maintained through a series of regulatory pathways. Mitochondrial homeostasis is dynamically regulated, mainly via key processes such as mitochondrial fission, mitochondrial fusion and mitophagy; however, mitochondrial processes are prone to dysregulation. Mitochondrial fission and fusion and mitophagy are intimately related to ferroptosis. Therefore, investigations into the dynamic regulation of mitochondrial processes during ferroptosis are important to provide a better understanding of the development of disease. In this paper, we systematically summarized changes in ferroptosis, mitochondrial fission and fusion and mitophagy to promote an in-depth understanding of the mechanism underlying ferroptosis and provide a corresponding reference for the treatment of related diseases.

Identification of key microRNAs in exosomes derived from patients with the severe acute pancreatitis.

OBJECTIVE: Exosomes have been identified as important carriers of various genetic materials, including microRNAs (miRNAs). Increasing evidence indicates that the course of severe acute pancreatitis (SAP) is associated with miRNAs transported by exosomes. We aimed to identify the signature miRNAs as biomarkers of SAP. METHODS: We obtained exosomes from the SAP patients' blood. After separation, purification, and identification, we performed high-throughput sequencing and screened the differentially expressed(DE) miRNAs in the exosomes. Bioinformatics analysis was performed to identified the target genes of the miRNAs and the pathways enriched based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and selected the key miRNAs related to SAP. Total RNA was extracted from patient serum exosomes to detect the expression levels of the selected miRNAs in exosomes of three experimental groups (mild -, moderately severe -, and severe AP) and a control group, using Real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: 272 DE miRNAs were identified between SAP and control group. Using bioinformatics analysis, we determined that the functions of the target genes were enriched in six signaling pathways including focal adhesion. Based on this, seven candidate signature miRNAs were selected: miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, and miR-583. The RT-qPCR results of the seven miRNAs in the SAP group were consistent with the sequencing results. CONCLUSION: Exosome-derived miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, miR-583 are positively correlated with SAP, which might provide new insights into the pathogenesis of SAP and serve as the biomarkers of SAP.

[Study on genetic transformation of antigen G3VP7 gene of human rotavirus in peanut].

In order to increase the expression level of target gene and to simplify the purifying process of separation and purification, we performed the transgenetic research of antigen VP7 gene into peanut via Agrobacterium tumefaciens. The plant binary expression vector is pBOG3VP7 harboring fusion gene oleosin-vp7, which is promoted by ole-promoter. Cotyledon nodes were used as transformation recipients. Transformed individuals were obtained through selection on medium containing 125 mg L-1 Kan. Integration of transgenes was assessed by PCR amplification and PCR-Southern blot hybridization. Taking pBOG3VP7 plasmid as positive control, non-transformed peanut as negative control. 6 plants among 11 plants grown up through seletion medium were detected by PCR and the rate of positive plants is 54.5%. PCR positive plants were further analysed by PCR-Southern blot hybridization. The results showed that 3 plants have DNA bloting bands. The results also showed that the foreign gene was integrated into genome of transformed peanuts. Elevated expression of rotavirus VP7 antigen in transgenic peanuts was a critical factor in the development of efficient and cheap plant oral vaccine.

Comprehensive evaluation method of the poultry house indoor environment based on gray relation analysis and analytic hierarchy process.

Due to the antagonism and synergy among environmental factors in the poultry house, the influence process becomes extremely complex. As a result, it is difficult to predict and evaluate the degree of such influence accurately. In this paper, we study the poultry house environment factor and its relationship with poultry production performance, using the gray relation analysis (GRA) to filtrate the main factors that influence the evaluation of the poultry house environment. Put forward using the gray relation degree (GRD) to improve the method for structuring the judgment matrix, and weights are more objective and reasonable. The evaluation index system and evaluation model are constructed through the analytic hierarchy process (AHP). It is expected that the comprehensive evaluation of the indoor environment status of the poultry house can guide the optimization of the environmental control in the poultry house and obtain better production indicators of the poultry. In this study, the experimental broiler house was enclosed in autumn. Because of the ventilation system, the indoor environment is still affected by the outdoor environment. The top 3 in the calculation of weights were outdoor environment (0.4315), indoor temperature (0.2384), and indoor air quality (0.1687), which were consistent with experience. From October 24 to 27, the environmental evaluation values of the experimental broiler house were {2.4367, 2.8149, 2.3857, 2.5669}, that is, the evaluation results were {good, good, good, good}; consistent with the expert manual judgment. The correctness and practicability of the proposed method were verified. This paper provides a scientific basis for environmental evaluation and environmental control in the poultry house.

Investigation on the antitumor effects of paeonol against renal cell carcinoma based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Renal cell carcinoma (RCC) is the most common cancer of the urinary system, the current treatments for RCC are unsatisfactory. Paeonol is the main pharmacologically active ingredient of the traditional Chinese medicine (TCM) moutan cortex (Paeonia suffruticosa Andrews) and Paeonia albiflora Pall, and has been used in TCM to treat various diseases including cancer. However, the underlying therapeutic mechanisms of paeonol in RCC have not been investigated yet. AIM OF THE STUDY: This study aimed to explore the potential antitumor effects and mechanisms of paeonol on RCC based on network pharmacology and experimental validation. MATERIALS AND METHODS: Network pharmacological analysis was performed to predict the potential targets and mechanism of paeonol against RCC. The antitumor effects and the priority targets of paeonol against RCC were further assessed by in vitro experiments. RESULTS: 104 intersection targets shared by paeonol and RCC were collected, 15 hub genes were obtained, among these genes, VEGFA expression was higher in RCC, and the higher expression of IL-6 or lower expression of AKT1, JUN, MAPK1, and MAPK8 were correlated to the shorter overall survival (OS) in RCC patients. GO and KEGG analyses suggested that the genes were mainly enriched in the positive regulation of cell death and apoptosis pathway. In vitro experiments showed that paeonol inhibited 786-O cell proliferation, migration, invasion, and promoted apoptosis. When 786-O cells were treated with paeonol, the expression of Bax increased while Bcl-2 and VEGFA decreased. CONCLUSION: The present study demonstrated that paeonol might play an essential role in RCC by regulating cell proliferation, apoptosis, metastasis, and invasion through the Bcl-2/Bax signaling pathway and VEGFA, providing a theoretical and experimental scientific basis for future investigations of the antitumor effects of paeonol against RCC.

Microclimate environment model construction and control strategy of enclosed laying brooder house.

The growth performance and health of chicks can be significantly improved by a suitable microclimate in brooder houses. However, the microclimate of the chicken house is affected by factors such as its structure and the heat dissipation of chickens, making it is difficult to establish an accurate mathematical model and achieve effective regulation. In this paper, the environmental data acquisition system of enclosed chick brooder house was established by analyzing various environmental factors in brooder houses. According to the structural characteristics of brooder houses and the growth environment of chicks and other parameters, the microclimate simulation model of brooder houses was established using the physical law of energy balance. The coefficient of determination R2 (R-square) between simulated temperature and humidity output value and measured value was 0.7634 and 0.9740, respectively, and Root Mean Square Error (RMSE) was 1.55°C and 2.61%, respectively. The correctness of the simulation model was verified. On the basis of established microclimate models, a simulation model of fuzzy decoupling Proportion Integration Differentiation (PID) control in chicken house environments was established for the strong coupling between temperature control and general risk control system in chicken houses. Different control strategies were generated by fuzzy and logical reasoning about multiple environmental factors. The compensation coefficient was added to optimize the environmental regulation system of brooder houses. The temperature maximum deviation between the set value and the fuzzy decoupling PID controller was 0.5°C, the maximum relative error was 2.7%, the maximum deviation of relative humidity between the set value and the fuzzy decoupling PID controller was 4.93%, the maximum relative error was 10.49%.The simulation results show the control strategy meets the temperature and humidity control requirements, verify the effectiveness of the control strategy and model. The experimental results can guide the actual environmental control of brooder houses.

Prognostic biomarkers of pancreatic cancer identified based on a competing endogenous RNA regulatory network.

Background: Pancreatic cancer is an insidious and heterogeneous malignancy with poor prognosis that is often locally unresectable. Therefore, determining the underlying mechanisms and effective prognostic indicators of pancreatic cancer may help optimize clinical management. This study was conducted to develop a prognostic model for pancreatic cancer based on a competing endogenous RNA (ceRNA) network. Methods: We obtained transcriptomic data and corresponding clinicopathological information of pancreatic cancer samples from The Cancer Genome Atlas (TCGA) database (training set). Based on the ceRNA interaction network, we screened candidate genes to build prediction models. Univariate Cox regression analysis was performed to screen for genes associated with prognosis, and least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to construct a predictive model. A receiver operating characteristic (ROC) curve was drawn, and the C-index was calculated to evaluate the accuracy of the prediction model. Furthermore, we downloaded transcriptomic data and related clinical information of pancreatic cancer samples from the Gene Expression Omnibus database (validation set) to evaluate the robustness of our prediction model. Results: Eight genes (ANLN, FHDC1, LY6D, SMAD6, ACKR4, RAB27B, AUNIP, and GPRIN3) were used to construct the prediction model, which was confirmed as an independent predictor for evaluating the prognosis of patients with pancreatic cancer through univariate and multivariate Cox regression analysis. By plotting the decision curve, we found that the risk score model is an independent predictor has the greatest impact on survival compared to pathological stage and targeted molecular therapy. Conclusions: An eight-gene prediction model was constructed for effectively and independently predicting the prognosis of patients with pancreatic cancer. These eight genes identified show potential as diagnostic and therapeutic targets.

Dimethyl Fumarate Combined With Vemurafenib Enhances Anti-Melanoma Efficacy via Inhibiting the Hippo/YAP, NRF2-ARE, and AKT/mTOR/ERK Pathways in A375 Melanoma Cells.

Melanoma is a deadly form of skin cancer with high rates of resistance to traditional chemotherapy and radiotherapy. BRAF inhibitors (BRAFi) can achieve initial efficacy when used to treat melanoma patients, but drug resistance and relapse are common, emphasizing the need for new therapeutic strategies. Herein, we reported that combination of dimethyl fumarate (DMF) and vemurafenib (Vem) inhibited melanoma cell proliferation more significantly and induced more cell death than single agent did both in vitro and in vivo. DMF/Vem treatment induced cell death through inhibiting the expression and transcriptional activity of NRF2 thereby resulting in more reactive oxygen species (ROS) and via inhibiting the expression of YAP, a key downstream effector of Hippo pathway. DMF/Vem treatment also reduced phosphorylation of AKT, 4EBP1, P70S6K and ERK in AKT/mTOR/ERK signaling pathways. RNA-seq analysis revealed that DMF/Vem treatment specifically suppressed 4561 genes which belong to dozens of cell signaling pathways. These results indicated that DMF/Vem treatment manifested an enhanced antitumor efficacy through inhibiting multiple cell signaling pathways, and thus would be a novel promising therapeutic approach targeted for melanoma.

Dynamics of carbon stocks of different pools in Huzhong National Nature Reserve, Northeast China under the disturbance of various severity fires.

In this study, the FireBGCv2 model was used to simulate the dynamics of forest carbon pools of Huzhong Nature Reserve within the next 100 years under various forest fire severity scena-rios. The aim of this study was to explore the responses of different forest carbon pools to fire disturbance, and to provide scientific basis for forest fuel management. The results showed that forest fire significantly reduced forest carbon storage, with the greatest reduction under the scenario of high-severity forest fire. Fire disturbance affected carbon storage in different pools, and relocated carbon among those pools. Forest fire disturbance reduced carbon storage of living trees and duff, increased that of coarse woody debris in the early and middle stages of simulation, and decreased that in late stage. The carbon storage of shrub and herb strata increased significantly in the late simulation period. The higher the fire severity, the lower the carbon storage of living tree and shrub-herb carbon pools, with snag and coarse woody debris showing the opposite trend. The impact of forest fire disturbance on the total carbon pool distribution was as follows: forest fire increased the proportion of shrub and herb strata, snag, coarse woody debris and soil carbon pool, and reduced the proportion of living tree and duff. The higher severity forest fire was, the lower the proportion of carbon pool of shrub-herb, and the higher the proportion of carbon pool of coarse wood debris. The severity of forest fire had less impact on the proportion of other carbon pools. In addition, our results demonstrated periodic change of litter carbon that reached a high value within 20 years and then dropped to a low value within 10 years. Our results could provide sound basis for determining the forest fuel treatment interval. We suggested performing prescribed burning every 20 years in the Great Xing'an Mountains area to protect forest resources.