Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity.

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Prediction of Patient Survival with Psoas Muscle Density Following Transjugular Intrahepatic Portosystemic Shunts: A Retrospective Cohort Study.

BACKGROUND Psoas muscle density (PMD) as a nutritional indicator is a tool to evaluate sarcopenia, which is commonly diagnosed in patients with liver cirrhosis. However, there are limited data on its role in patients who have received a transjugular intrahepatic portosystemic shunt (TIPS). We aimed to determine the utility of PMD in predicting mortality of patients with TIPS implantation and to compare the clinical value of PMD, Child-Pugh score, model for end-stage liver disease (MELD) score, and MELD paired with serum sodium measurement (MELD-Na) score in predicting post-TIPS survival in 1 year. MATERIAL AND METHODS This retrospective study included 273 patients who met the criteria for study inclusion. All participants underwent computed tomography (CT) scans, Child-Pugh score evaluation, MELD-Na scoring, and MELD scoring. Post-TIPS survival time was estimated using the Kaplan-Meier survival curve. The prognostic values of scoring models such as the Child-Pugh score, MELD, MELD-Na, and PMD were evaluated using receiver operating characteristic curves. RESULTS During the 1-year follow-up period, 31 of 273 (11.36%) post-TIPS patients died. Multivariate analysis identified PMD as an independent protective factor. PMD showed a good ability to predict the occurrence of an endpoint within 1 year after TIPS. The area under the receiver operating characteristic curves for PMD, Child-Pugh score, MELD score, and MELD-Na for predicting mortality were, respectively, 0.72 (95% confidence interval [CI]: 0.663-0.773), 0.59 (95% CI: 0.531-0.651), 0.60 (95% CI: 0.535-0.655), and 0.58 (95% CI: 0.487-0.608). CONCLUSIONS PMD has appreciable clinical value for predicting the mortality of patients with TIPS implantation. In addition, PMD is superior to established scoring systems for identifying high-risk patients with a poor prognosis.

Development of a scale for the impact of emotion management on young athletes' training efficiency.

In this study, we developed a scale to evaluate emotion management and its benefits for young athletes in China, and to analyze the impact of emotion management on their training efficiency. Following an extensive literature review, we used AMOS structural equation model software to develop a scale for evaluating the effects and benefits of emotion management on young athletes' training efficiency. Results showed that young athletes' emotion management training and its benefits can be divided into five dimensions: benefit evaluation, emotional cognition, emotion influence, emotion control, and emotion regulation. The internal consistency reliability of the formal scale was 0.895, and the internal consistency reliability of each subscale was between 0.734 and 0.901. The split-half reliability was 0.769, and the split-half reliability of each subscale was between 0.623 and 0.864. The KMO value was 0.904, P = 0.00 (p < 0.05), and the cumulative interpretation rate was 61.782 % of the total variance. The lowest factor load of a scale item was 0.436, and the highest factor load was 0.846. The common degree of all items was between 0.402 and 0.762, indicating that the scale has good validity. A SEM model verified that the scale has good construct validity. Significant correlational differences were observed among the levels. The results of the SEM structural equation model analysis showed that the model's NC = 2.660 (1 < NC < 3 indicates that the model has a simple fit), PGFI = 0.722, PNFI = 0.699, IFI = 0.851, PRA = 0.927, RMR = 0.006, and RMSEA = 0.07, thus, these indexes reached the standard of excellent model fitting. The strongest correlation was found between emotional cognition and benefit evaluation (R = 0.690), and the weakest correlation was found between emotion influence and benefit evaluation (R = 0.079). These findings provide a basis for measuring the effect of emotion management on training efficiency in the training process of young athletes and offer a theoretical reference for their emotional development while in training.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY: The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION: In patients with pancreatic swelling, the possibility of AIP should be considered.

Prognostic insights and immune microenvironment delineation in acute myeloid leukemia by ferroptosis-derived signature.

Acute myeloid leukemia (AML) represents as a prevalent and formidable hematological malignancy, characterized by notably low 5-year survival rates. Ferroptosis has been found to be correlated with cancer initiation, therapeutic response, and clinical outcome. Nevertheless, the involvement of Ferroptosis-related genes (FRGs) in AML remains ambiguous. Five independent AML cohorts totaling 1,470 (GSE37642, GSE12417, GSE10358, Beat-AML, and TCGA-AML) patients with clinical information were used to systematically investigated the influence of these FRGs expression on outcome and tumor microenvironment. The integration of these datasets led to the subdivision into training and validation sets. Nineteen FRGs were identified as correlated with the overall survival (OS) of AML patients, primarily enriched in ferroptosis, fatty acid metabolism, and leukemia-related signaling pathways. The prognostic signature, consisting of 11 FRGs, was formulated using LASSO-Cox stepwise regression analysis. Patients with high-risk scores exhibited reduced survival compared to those in the low-risk group. The receiver operating characteristic (ROC) analysis underscored the signature's robust predictive accuracy. The high predictive efficacy was confirmed by both internal and external validation datasets. Leukemia and signaling related to immune regulation were mainly enriched pathways of the differentially expressed genes by comparing high- and low-risk groups. The immune composition deconvolution might indicate an immunosuppressive niche in the high-risk patients. The pRRophetic algorithm exploration unveiled chemical drugs with potentially sensitivity among patients in both groups. Collectively, our study developed a ferroptosis-derived prognostic signature that provides the OS prediction and identifies the immune microenvironment for AML patients on large-scale AML cohorts.

Molecular subtyping of acute myeloid leukemia through ferroptosis signatures predicts prognosis and deciphers the immune microenvironment.

Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancies with a low 5-year survival rate and high rate of relapse. Developing more efficient therapies is an urgent need for AML treatment. Accumulating evidence showed that ferroptosis, an iron-dependent form of programmed cell death, is closely correlated with cancer initiation and clinical outcome through reshaping the tumor microenvironment. However, understanding of AML heterogeneity based on extensive profiling of ferroptosis signatures remains to be investigated yet. Herein, five independent AML transcriptomic datasets (TCGA-AML, GSE37642, GSE12417, GSE10358, and GSE106291) were obtained from the GEO and TCGA databases. Then, we identified two ferroptosis-related molecular subtypes (C1 and C2) with distinct prognosis and tumor immune microenvironment (TIME) by consensus clustering. Patients in the C1 subtype were associated with favorable clinical outcomes and increased cytotoxic immune cell infiltration, including CD8+/central memory T cells, natural killer (NK) cells, and non-regulatory CD4+ T cells while showing decreased suppressive immune subsets such as M2 macrophages, neutrophils, and monocytes. Functional enrichment analysis of differentially expressed genes (DEGs) implied that cell activation involved in immune response, leukocyte cell-cell adhesion and migration, and cytokine production were the main biological processes. Phagosome, antigen processing and presentation, cytokine-cytokine receptor interaction, B-cell receptor, and chemokine were identified as the major pathways. To seize the distinct landscape in C1 vs. C2 subtypes, a 5-gene prognostic signature (LSP1, IL1R2, MPO, CRIP1, and SLC24A3) was developed using LASSO Cox stepwise regression analysis and further validated in independent AML cohorts. Patients were divided into high- and low-risk groups, and decreased survival rates were observed in high- vs. low-risk groups. The TIME between high- and low-risk groups has a similar scenery in C1 vs. C2 subtypes. Single-cell-level analysis verified that LSP1 and CRIP1 were upregulated in AML and exhausted CD8+ T cells. Dual targeting of these two markers might present a promising immunotherapeutic for AML. In addition, potential effective chemical drugs for AML were predicted. Thus, we concluded that molecular subtyping using ferroptosis signatures could characterize the TIME and provide implications for monitoring clinical outcomes and predicting novel therapies.

Chinese medical staff's knowledge, attitudes and practices towards breast cancer patients' sexual health management: A cross-sectional study.

Objective: The objective of this research was to assess the level and determinants of medical personnel's knowledge, attitudes, and practices regarding the management of sexual health in breast cancer survivors residing in western China. Background: Sexual well-being is a crucial aspect of one's overall satisfaction with life. Once female sexual dysfunction (FSD) occurs, it will affect patients' satisfaction and life quality seriously. In all healthcare settings, the management of sexual health relies heavily on the vital contribution of medical personnel. Nevertheless, the sexual requirements of individuals with breast cancer are still partially unmet. Design: A web-based questionnaire was used to conduct a multi-centered, cross-sectional study involving medical staff from 26 hospitals in nine cities of Guizhou Province, China. Methods: Data was gathered from healthcare professionals using a validated tool, the knowledge, attitudes, practices assessment scale for managing the sexual health of breast cancer patients in medical staff. This tool was used to evaluate the knowledge, attitudes, and practices of medical staff regarding sexual health management. Results: In this study, a grand total of 3181 healthcare professionals took part. The overall KAP scores, including knowledge, attitudes, and practices, were 47.15 ± 11.91, 72.55 ± 12.56, and 58.61 ± 11.45, respectively. Three variables exhibited a strong and favorable correlation. The study identified significant concerns regarding the limited understanding of medical personnel regarding effective strategies for enhancing sexual health function in breast cancer patients, as well as their diminished confidence in addressing FSD. The scores of knowledge, attitudes, and practices related to sexual health management were significantly influenced by whether or not training was received. Conclusions: The study results emphasize the importance of adopting a holistic approach to enhance the understanding, perspectives, and behaviors of healthcare professionals regarding the management of sexual health. In addition to enhancing the standard of care for individuals with breast cancer.

LEF1 enhances ß-catenin transactivation through IDR-dependent liquid-liquid phase separation.

Wnt/ß-catenin signaling plays a crucial role in cancer development, primarily activated by ß-catenin forming a transcription complex with LEF/TCF in the nucleus and initiating the transcription of Wnt target genes. Here, we report that LEF1, a member of the LEF/TCF family, can form intrinsically disordered region (IDR)-dependent condensates with ß-catenin both in vivo and in vitro, which is required for ß-catenin-dependent transcription. Notably, LEF1 with disrupted IDR lost its promoting activity on tumor proliferation and metastasis, which can be restored by substituting with FUS IDR. Our findings provide new insight into the essential role of liquid-liquid phase separation in Wnt/ß-catenin signaling and present a potential new target for cancer therapy.

Identification of Molecular Targets and Potential Mechanisms of Yinchen Wuling San Against Head and Neck Squamous Cell Carcinoma by Network Pharmacology and Molecular Docking.

Head and neck squamous cell carcinoma (HNSCC) represents one of the most malignant and heterogeneous tumors, and the patients have low 5-year survival. Traditional Chinese medicine (TCM) has been demonstrated as an effective complementary and/or alternative therapy for advanced malignancies including HNSCC. It has been noted that several herbs that are used for preparing Yinchen Wuling San (YWLS) have anti-tumor activities, whereas their mechanisms of action remain elusive. In this study, network pharmacology and molecular docking studies were employed to explore the underlying mechanisms of action of YWLS against HNSCC. The 58 active ingredients from six herbs used for YWLS and their 506 potential targets were screened from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction database. A total of 2,173 targets associated with HNSCC were mainly identified from the DisGeNET and GeneCards databases. An active components-targets-disease network was constructed in the Cytoscape. Top 20 hub targets, such as AKT1, EGFR, TNF, ESR1, SRC, HSP90AA1, MAPK3, ERBB2, and CCND1, were identified by a degree in the protein-protein interaction (PPI) network. Gene functional enrichment analysis showed that PI3K-AKT, MAPK, Ras, TNF, and EGFR were the main signaling pathways of YWLS in treating HNSCC. There were 48 intersected targets such as EGFR, AKT1, and TNF that were associated with patients' outcomes by the univariate Cox analysis, and most of them had increased expression in the tumor as compared to normal tissues. The area under curves of receiver operating characteristic indicated their diagnostic potential. Inhibition of these survival-related targets and/or combination with EGFR or AKT inhibitors were promising therapeutic options in HNSCC. The partial active components of YWLS exhibited good binding with the hub targets, and ADME analysis further evaluated the drug-likeness of the active components. These compounds and targets identified in this study might provide novel treatment strategies for HNSCC patients, and the subsequent work is essential to verify the underlying mechanisms of YWLS against HNSCC.

Biological Breakdown of Sports in Athletics Based on Multimedia Image Acquisition Techniques.

This paper provides an in-depth analysis and study of the decomposition of sports biology of athletics events through multimedia image acquisition techniques. The proposed design uses SOPC hardware-software collaboration technology, which makes full use of the parallelism of hardware as well as the flexibility of software to essentially improve the speed of image processing and greatly improve the efficiency of image processing. The high speed and parallelism of hardware are used to realize the image acquisition part with high timing requirements and the preprocessing algorithm with a large number of operations and strong repetition, in addition to the difficulties of many initialization configuration parameters of each peripheral. Additionally, the need for frequent adjustment of peripheral working parameters is solved by making full use of the scalability and flexibility of software, and the control signals output by software can coordinate the work of each hardware module to ensure that each module of the system cooperates. It is also possible to coordinate the work of each hardware module through the control signal output from the software to ensure that each module of the system cooperates and operates in an orderly and efficient manner and provides the possibility of realizing a higher level of the image processing algorithm. The system includes four main factors: swinging action, supporting action, vacating action, and speed rhythm. Based on this system, 14 key kinematic indicators were selected to reflect the technical status of the youth walkers. The landing angle decreased with the increase of speed, and the landing technique was insufficient; it had better control of the large and small arm angle, and their stride width was open, while the other four athletes showed increased tension in the hip joint and upper limb with the increase of walking speed, as well as the wrong action of forward and internal rotation of the large and small arms.

Predictive biomarkers for response to omalizumab in patients with severe allergic asthma: a meta-analysis.

BACKGROUND: Predicting omalizumab treatment response has been a challenge and significant aspect for selecting suitable severe allergic asthma patients for omalizumab use. OBJECTIVE: To determine which domains of pretreatment baseline characteristics predict omalizumab treatment response among asthmatic patients. METHODS: Electronic bases were searched for eligible studies that reported potential biomarkers that could predict omalizumab responsiveness and efficacy. Patients who accepted omalizumab treatment were stratified into responders and non-responders. WMD, OR, and their 95%CI were used to access the differences between those omalizumab receivers. Sensitivity analysis and subgroup analysis were conducted for potential heterogeneity. RESULTS: A total of 41 studies evaluating efficacy predictors of omalizumab were included in this meta-analysis. The pooled results showed that omalizumab responders had significantly younger age in the adult subgroup, higher pretreatment total serum IgE level, percent predicted FEV1 and FeNO than that non-responder. We further confirmed that higher blood eosinophil counts and total serum IgE levels are useful markers for selecting asthma patients who may benefit more from omalizumab. CONCLUSIONS: Pre-treatment blood eosinophil counts and total serum IgE level can be a useful efficacy predictor in selecting allergic asthma patients for omalizumab treatment.

Identification of survival-related alternative splicing signatures in acute myeloid leukemia.

Aberrant RNA alternative splicing (AS) variants play critical roles in tumorigenesis and prognosis in human cancers. Here, we conducted a comprehensive profiling of aberrant AS events in acute myeloid leukemia (AML). RNA AS profile, including seven AS types, and the percent spliced in (PSI) value for each patient were generated by SpliceSeq using RNA-seq data from TCGA. Univariate followed by multivariate Cox regression analysis were used to identify survival-related AS events and develop the AS signatures. A nomogram was developed, and its predictive efficacy was assessed. About 27,892 AS events and 3,178 events were associated with overall survival (OS) after strict filtering. Parent genes of survival-associated AS events were mainly enriched in leukemia-associated processes including chromatin modification, autophagy, and T-cell receptor signaling pathway. The 10 AS signature based on seven types of AS events showed better efficacy in predicting OS of patients than those built on a single AS event type. The area under curve (AUC) value of the 10 AS signature for 3-year OS was 0.91. Gene set enrichment analysis (GSEA) confirmed that these survival-related AS events contribute to AML progression. Moreover, the nomogram showed good predictive performance for patient's prognosis. Finally, the correlation network of AS variants with splicing factor genes found potential important regulatory genes in AML. The present study presented a systematic analysis of survival-related AS events and developed AS signatures for predicting the patient's survival. Further studies are needed to validate the signatures in independent AML cohorts and might provide a promising perspective for developing therapeutic targets.

Identification of a survival-related signature for sarcoma patients through integrated transcriptomic and proteomic profiling analyses.

Sarcoma (SARC) represents a group of highly histological and molecular heterogeneous rare malignant tumors with poor prognosis. There are few proposed classifiers for predicting patient's outcome. The Cancer Proteome Atlas (TPCA) and The Cancer Genome Atlas (TCGA) databases provide multi-omics datasets that enable a comprehensive investigation for this disease. The proteomic expression profile of SARC patients along with the clinical information was downloaded. 55 proteins were found to be associated with overall survival (OS) of patients using univariate Cox regression analysis. We developed a prognostic risk signature that comprises seven proteins (AMPKALPHA, CHK1, S6, ARID1A, RBM15, ACETYLATUBULINLYS40, and MSH6) with robust predictive performance using multivariate Cox stepwise regression analysis. Additionally, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters. Patients in high-risk group also have worse progression free intervals (PFI) than that of patients in low-risk group, but not for disease free intervals (DFI). The signature was validated using transcriptomic profile of SARC patients from TCGA. Potential mechanisms between high- and low-risk groups were identified using differentially expressed genes (DEGs) analysis. These DEGs were primarily enriched in RAS and MPAK signaling pathways. The signature protein molecules are candidate biomarkers for SARC, and the analysis of computational biology in tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinctly immune landscapes of high- and low-risk patients. Together, we constructed a prognostic signature for predicting outcomes for SARC integrating proteomic and transcriptomic profiles, this might have value in guiding clinical practice.

Serum Vitamin D Level and the Risk of Urinary Tract Infection in Children: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to evaluate the association between serum vitamin D concentration and the risk of urinary tract infection (UTI) in children. Human studies reported the serum vitamin D level in children with UTI and healthy controls were collected from PubMed, Scopus, Embase, and Cochrane databases. The strictly standardized mean difference (SSMD) and 95% confidence interval (CI) were calculated to evaluate the relationship between serum vitamin D levels and risk of UTI. The results of analysis showed that serum vitamin D levels in children with UTI were significantly lower than healthy control children (SSMD: 0.891, 95% CI: 0.707-1.075, p < 0.000; SSMD: 0.797, 95% CI: 0.500-1.094, p < 0.000, respectively). It can be concluded that there is a significant negative relationship between serum vitamin D level and risk of UTI in children.

Prognosis and Characterization of Immune Microenvironment in Acute Myeloid Leukemia Through Identification of an Autophagy-Related Signature.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has an unfavorable outcome and a high rate of relapse. Autophagy plays a vital role in the development of and therapeutic responses to leukemia. This study identifies a potential autophagy-related signature to monitor the prognoses of patients of AML. Transcriptomic profiles of AML patients (GSE37642) with the relevant clinical information were downloaded from Gene Expression Omnibus (GEO) as the training set while TCGA-AML and GSE12417 were used as validation cohorts. Univariate regression analyses and multivariate stepwise Cox regression analysis were respectively applied to identify the autophagy-related signature. The univariate Cox regression analysis identified 32 autophagy-related genes (ARGs) that were significantly associated with the overall survival (OS) of the patients, and were mainly rich in signaling pathways for autophagy, p53, AMPK, and TNF. A prognostic signature that comprised eight ARGs (BAG3, CALCOCO2, CAMKK2, CANX, DAPK1, P4HB, TSC2, and ULK1) and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. High-risk patients were found to have significantly shorter OS than patients in low-risk group. The signature can be used as an independent prognostic predictor after adjusting for clinicopathological parameters, and was validated on two external AML sets. Differentially expressed genes analyzed in two groups were involved in inflammatory and immune signaling pathways. An analysis of tumor-infiltrating immune cells confirmed that high-risk patients had a strong immunosuppressive microenvironment. Potential druggable OS-related ARGs were then investigated through protein-drug interactions. This study provides a systematic analysis of ARGs and develops an OS-related prognostic predictor for AML patients. Further work is needed to verify its clinical utility and identify the underlying molecular mechanisms in AML.

The tumor therapy landscape of synthetic lethality.

Synthetic lethality is emerging as an important cancer therapeutic paradigm, while the comprehensive selective treatment opportunities for various tumors have not yet been explored. We develop the Synthetic Lethality Knowledge Graph (SLKG), presenting the tumor therapy landscape of synthetic lethality (SL) and synthetic dosage lethality (SDL). SLKG integrates the large-scale entity of different tumors, drugs and drug targets by exploring a comprehensive set of SL and SDL pairs. The overall therapy landscape is prioritized to identify the best repurposable drug candidates and drug combinations with literature supports, in vitro pharmacologic evidence or clinical trial records. Finally, cladribine, an FDA-approved multiple sclerosis treatment drug, is selected and identified as a repurposable drug for treating melanoma with CDKN2A mutation by in vitro validation, serving as a demonstrating SLKG utility example for novel tumor therapy discovery. Collectively, SLKG forms the computational basis to uncover cancer-specific susceptibilities and therapy strategies based on the principle of synthetic lethality.

[Anticancer activities of curcumin on human hepatocarcinoma cell line Sk-hep-1].

To study the anticancer activities of curcumin on human hepatocarcinoma cell line Sk-hep-1 and its related molecular mechanism which has not been elucidated. In the present study,we showed that curcumin inhibited proliferation of Sk-hep-1 cells in a dose-dependent manner through MTF assay. The effect of curcumin on apoptosis in Sk-hep-1 cells was investigated by DAPI staining and the various apoptosis was observed in hepatocarcinoma cell lines Sk-hep-1, HepG2 and Hep3B, but not in normal liver cell line Chang's liver with curcumin treatment. Cell cycle analysis results showed that curcumin treatment resulted in dramatic accumulation of Sk-hep-1 cells at the G0/G1 or G2/M phase. The effect of curcumin on the expression of anti-apoptosis genes (Survivin and BCl-xL) and drug resistance genes (DRG2 and MDR1) was studied by reverse transcription-polymerase chain reaction (RT-PCR). The expression of MDR1 mRNA was significantly decreased in Sk-hep-1 cells treated with curcumin, while no alterations in the amount of DRG2 and anti-apoptosis genes' mRNA levels were found. These results indicate that curcumin is able to inhibit proliferation and induce apoptosis in Sk-hep-1 cells and it may cause by down-regulating the expression of MDR1 mRNA.

PPARα Agonist WY-14643 Relieves Neuropathic Pain through SIRT1-Mediated Deacetylation of NF-κB.

Inflammation caused by neuropathy contributes to the development of neuropathic pain (NP), but the exact mechanism still needs to be understood. Peroxisome proliferator-activated receptor α (PPARα), an important inflammation regulator, might participate in the inflammation in NP. To explore the role of PPARα in NP, the effects of PPARα agonist WY-14643 on chronic constriction injury (CCI) rats were evaluated. The results showed that WY-14643 stimulation could decrease inflammation and relieve neuropathic pain, which was relative with the activation of PPARα. In addition, we also found that the SIRT1/NF-κB pathway was involved in the WY-14643-induced anti-inflammation in NP, and activation of PPARα increased SIRT1 expression, thus reducing the proinflammatory function of NF-κB. These data suggested that WY-14643 might serve as an inflammation mediator, which may be a potential therapy option for NP.

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory- and immune-related processes. "Cytokine-cytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high- and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.

Cloning and characterization of the promoter of the 9-cis-epoxycarotenoid dioxygenase gene in Arachis hypogaea L.

We cloned the promoter of the 9-cis-epoxycarotenoid dioxygenase gene from Arachis hypogaea L. beta-Glucuronidase (GUS) histochemical staining and GUS activity assay indicated that the activity of the promoter was exhibited predominantly in the leaves and enhanced by water and NaCl stresses, and by application of abscisic acid (ABA) and salicylic acid (SA) in transgenic Arabidopsis. Moreover, two novel ABRE-like (abscisic acid response element) elements were identified in the promoter region.