Network pharmacology combined with an experimental validation study to reveal the effect and mechanism of Lonicera japonica Thunb. extracts against immunomodulation.

Lonicera japonica Thunb. (LJT) is known for its valuable medicinal properties that highlight its potential application in the pharmaceutical and health food industry. We predict that LJT polyphenols by network pharmacology may be involved in immunomodulation, and the study of LJT polyphenols regulating immunity is still insufficient; therefore, we experimentally found that LJT enhances immunity by promoting the proliferation and phagocytic activity of RAW246.7 cells. A model of an immunosuppressed mouse was constructed using cyclophosphamide-induced, and LJT was extracted for the intervention. We found that LJT restored immune homeostasis in immune deficiency mice by inhibiting the abnormal apoptosis in lymphocytes, enhancing natural killer cell cytotoxicity, promoting T lymphocyte proliferation, and increasing the CD4+ and CD8+ T lymphocytes in quantity. Moreover, LJT treatment modulates immunity by significantly downregulating lipopolysaccharide-induced inflammation and oxidative stress levels. We verified the immunomodulatory function of LJT through both cell and animal experiments. The combination of potential-protein interactions and molecular docking later revealed that LJT polyphenols were associated with immunomodulatory effects on MAPK1; together, LJT intervention significantly modulates the immune, with the activation of MAPK1 as the underlying mechanism of action, which provided evidence for the utilization of LJT as a nutraceutical in immune function.

Prenatal diagnosis of 46,XX testicular disorder of sex development with SRY-positive: A case report and review of the literature.

We report a case of a fetus with 46,XX testicular disorder of sex development detected prenatally. This fetus was found abnormally due to non-invasive prenatal testing. Amniocentesis revealed SRY gene on the X chromosome of the fetus. The related literature was reviewed, and the advantages and limitations of various prenatal diagnostic techniques were discussed. The combination of non-invasive prenatal testing and various prenatal diagnostic techniques has enabled more fetuses with sex reversal to be detected.

Prediction of In-Flight Particle Properties and Mechanical Performances of HVOF-Sprayed NiCr-Cr3C2 Coatings Based on a Hierarchical Neural Network.

High-velocity oxygen fuel (HVOF) spraying is a promising technique for depositing protective coatings. The performances of HVOF-sprayed coatings are affected by in-flight particle properties, such as temperature and velocity, that are controlled by the spraying parameters. However, obtaining the desired coatings through experimental methods alone is challenging, owing to the complex physical and chemical processes involved in the HVOF approach. Compared with traditional experimental methods, a novel method for optimizing and predicting coating performance is presented herein; this method involves combining machine learning techniques with thermal spray technology. Herein, we firstly introduce physics-informed neural networks (PINNs) and convolutional neural networks (CNNs) to address the overfitting problem in small-sample algorithms and then apply the algorithms to HVOF processes and HVOF-sprayed coatings. We proposed the PINN and CNN hierarchical neural network to establish prediction models for the in-flight particle properties and performances of NiCr-Cr3C2 coatings (e.g., porosity, microhardness, and wear rate). Additionally, a random forest model is used to evaluate the relative importance of the effect of the spraying parameters on the properties of in-flight particles and coating performance. We find that the particle temperature and velocity as well as the coating performances (porosity, wear resistance, and microhardness) can be predicted with up to 99% accuracy and that the spraying distance and velocity of in-flight particles exert the most substantial effects on the in-flight particle properties and coating performance, respectively. This study can serve as a theoretical reference for the development of intelligent HVOF systems in the future.

Fetal hyperechoic kidney cohort study and a meta-analysis.

Objective: To investigate the positive rate of chromosomal and monogenic etiologies and pregnancy outcomes in fetuses with hyperechoic kidney, and to provide more information for genetic counseling and prognosis evaluation. Methods: We performed a retrospective analysis of 25 cases of hyperechoic kidney diagnosed prenatal in the Second Affiliated Hospital of Harbin Medical University and Harbin Red Cross Central Hospital (January 2017-December 2022). Furthermore, we conducted a meta-analysis of a series of hyperechoic kidneys (HEK) in the literature to assess the incidence of chromosomal and monogenic etiologies, mortality, and pooled odds ratio (OR) estimates of the association between the incidence of these outcomes and other associated ultrasound abnormalities. Results: 25 fetuses of HEK were enrolled in the cohort study, including 14 with isolated hyperechoic kidney (IHK) and 11 with non-isolated hyperechoic kidney (NIHK). Chromosomal aneuploidies were detected in 4 of 20 patients (20%). The detection rate of pathogenic or suspected pathogenic copy number variations (CNVs) was 29% (4/14) for IHK and 37% (4/11) for NIHK. Whole exome sequencing (WES) was performed in 5 fetuses, and pathogenic genes were detected in all of them. The rate of termination of pregnancy was 56% in HEK. 21 studies including 1,178 fetuses were included in the meta-analysis. No case of abnormal chromosome karyotype or (intrauterine death)IUD was reported in fetuses with IHK. In contrast, the positive rate of karyotype in NIHK was 22% and that in HEK was 20%, with the ORs of 0.28 (95% CI 0.16-0.51) and 0.25, (95% CI 0.14-0.44), respectively. The positive rate of (chromosome microarray analysis) CMA in IHK was 59% and that in NIHK was 32%, with the ORs of 1.46 (95% CI 1.33-1.62) and 0.48 (95% CI, 0.28-0.85), respectively. The positive rate of monogenic etiologies in IHK was 31%, with the OR of 0.80 (95% CI 0.25-2.63). In IHK, the termination rate was 21% and neonatal mortality was 13%, with the ORs of 0.26 (95% CI, 0.17-0.40), 1.72 (95% CI, 1.59-1.86), and that in NIHK was 63%, 0.15 (95% CI, 0.10-0.24); 11%, 0.12 (95% CI, 0.06-0.26), respectively. The intrauterine mortality in NIHK group was 2%, with the OR of 0.02 (95% CI, 0.01-0.05). HNF1B variant has the highest incidence (26%) in IHK. Conclusion: The positive rate of karyotype was 20% in HEK and 22% in NIHK. The positive rate of CMA was 32% in NIHK and 59% in IHK. The positive rate of IHK monogenic etiologies was 31%. HNF1B gene variation is the most common cause of IHK. The overall fetal mortality rate of NIHK is significantly higher than that of IHK. The amount of amniotic fluid, kidney size and the degree of corticomedullary differentiation have a great impact on the prognosis, these indicators should be taken into consideration to guide clinical consultation and decision-making.

Increased inflammatory mediators levels are associated with clinical outcomes and prolonged illness in severe COVID-19 patients.

OBJECTIVE: The purpose of this study was to identify potential predictors of clinical outcome in severe COVID-19 patients and to investigate the relationship between immunological parameters and duration of illness. METHODS: This single-center study retrospectively recruited 73 patients with severe or critical COVID-19. Immunological indicators include white blood cell count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, and circulating inflammatory mediators were observed for their association with disease severity, mortality and duration of illness of COVID-19. RESULTS: Serum inflammatory mediators levels of C-reactive protein (P = 0.015), interleukin 6 (IL-6) (P < 0.001), CX3CL1 (P < 0.001), D-dimer (P < 0.001) and procalcitonin (PCT) (P < 0.001) were increased in critical illness patients compared to those severe COVID-19 patients. CX3CL1 has the highest C-index (0.75) to predict in-hospital mortality in patients with COVID-19. Furthermore, this study shows for the first time that the duration of illness in severe COVID-19 patients is associated with serum levels of CX3CL1 (P = 0.037) and D-dimer (P = 0.014). CONCLUSION: CX3CL1, D-dimer, PCT, and IL-6 could effectively predict mortality in severe COVID-19 patients. In addition, only the circulating levels of CX3CL1 and D-dimer were significantly associated with duration of illness.

Testing the Reciprocal Effect between Value of Education, Time Investment, and Academic Achievement in a Large Non-Western Sample.

Many theories of motivation suggest that motivation and academic achievement reinforce each other over time, yet few longitudinal studies have examined behavioral pathways that may mediate interplay from motivation to achievement. Moreover, empirical studies so far have mostly focused on Western countries. In this study, we first examined whether students' value of education, as a measure of motivation, is reciprocally related to achievement (class rank and self-rated performance) in a sample of junior high schoolers in an East-Asian country (N = 3445, Korean Youth Panel Study). We tested this reciprocity using different statistical models. Second, we investigated whether the relation between motivation and achievement was mediated by time invested in learning. Reciprocal effects between value of education and academic achievement were found in classic cross-lagged panel models, but only unilateral effects (from achievement to value of education) were found when we used random-intercept and random-curve cross-lagged panel models. Adding the time investment variable, the reciprocal effect between value of education, time investment, and academic achievement was found with the random intercept model. In conclusion, the reciprocity between of motivation and achievement are more elusive than previous research suggested; further studies should be dedicated to scrutinizing its existence with various statistical models.

Iodine status and its association with prevalence of thyroid diseases in adults from Jiangxi Province, China.

BACKGROUND: Iodine is an essential element for the biosynthesis of thyroid-stimulating hormone (TSH). Both excessive and deficient iodine are major risk factors for thyroid diseases, including thyroid dysfunction, thyroid nodules, and thyroid autoimmunity (TAI). This study aimed to elucidate the relationship between iodine status and the prevalence of thyroid diseases through a national cross-sectional epidemiological survey in Jiangxi province (China). METHODS: This population-based, cross-sectional study enrolled 2636 Chinese local inhabitants who aged over 18 years old from April to August in 2015. Physical examination was performed and biochemical indices, urinary iodine concentration (UIC), and TSH level were measured. The Chi-square test, nonparametric test, and 4 multivariate logistic regression models adjusted for risk factors were applied to analysis. Spearman correlation coefficients were calculated to investigate the relationship between iodine intake level and the prevalence of thyroid diseases. RESULTS: The median UIC was 176.4 µg/L, and a significant difference was found in median UIC between men (182.45 µg/L) and women (169.25 µg/L) (P = 0.03). Among these study subjects, 14.4%, 44.5%, 26.1%, and 15.0% had deficient, adequate, more than adequate, and excessive iodine concentrations, respectively. The prevalence rates of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, thyroid nodules, and TAI were 0.91%, 0.57%, 0.34% and 7.89%, 9.45%, and 12.7%, respectively. Significant differences were found in iodine status, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), TSH, thyroid nodules, and TAI between men and women (P < 0.05). Compared with those with adequate UIC, subjects with excessive UIC had higher prevalence rates of thyroid dysfunction (odds ratio (OR) = 1.74, 95% confidence interval (CI): 1.40-2.54) and thyroid nodules (OR = 3.33, 95%CI 1.32-8.42). In addition, subjects with deficient and excessive UIC were at the higher risk of TAI compared with those with adequate UIC (OR = 1.68, 95%CI: 1.19-2.60; OR = 1.52, 95%CI: 1.04-2.96, respectively). UIC was positively correlated with the prevalence rates of thyroid nodules (r = -0.44, P < 0.01) and TAI (r = -0.055, P < 0.01). On the contrary, UIC was negatively correlated with the risk of thyroid dysfunction (r = -0.24, P > 0.05). CONCLUSION: Adult inhabitants from Jiangxi province in the TIDE study were in the adequate iodine status. Excessive iodine status was noted as a risk factor for thyroid dysfunction and thyroid nodules. In addition, both iodine deficiency and excessive iodine were risk factors for TAI.

Evodiamine exerts inhibitory roles in non­small cell lung cancer cell A549 and its sub­population of stem­like cells.

Evodiamine (EVO) is one of the main components extracted from Evodia rutaecarpa and has been reported to inhibit tumor growth by inhibiting proliferation and inducing apoptosis. Although the anticancer activity of evodiamine has been confirmed, the exact mechanism remains to be elucidated. In the present study, cancer stem-like cells (CSCs) were successfully enriched from A549 cells by being cultured in serum-free medium and characterized by detecting stemness markers. Expectedly, the addition of EVO inhibited proliferation, migration and invasion in A549 cells, demonstrating its inhibitory effects on the malignant behaviors of A549 cells. In CSCs derived from A549 cells, EVO treatment promoted cell proliferation while inhibiting migration and invasion. By detecting the hallmarks of the epithelial-mesenchymal transition (EMT), including E-cadherin, Vimentin, Slug and Snail via western blotting, it was revealed that EVO treatment inactivated the EMT process and potentially led to the loss of self-renewal capacity of CSCs and promoted proliferation. By activating the EMT using TGF-ß pretreatment, EVO treatment downregulated the hallmarks of the EMT and led to inactivation of the EMT, indicating its potential mechanism of regulating CSCs via the EMT pathway. The findings suggested that modulation of the self-renewal capacity of CSCs may affect malignant cancer behaviors following surgery. EVO exerts inhibitory effects not only on cancer cells but also on CSCs in non-small-cell lung cancer, and therefore could be used as a promising drug targeting CSCs.

The Effect of Educational Expectations on Children's Cognition and Depression.

Cognitive and psychological conditions in childhood will have an important impact on adult life. There is relatively little literature on the impact of educational expectations on children's cognition and psychological health from the perspective of urban and rural differences. Based on the cohort data of the CFPS from 2012 and 2016, this study screened a total of 994 children aged 10-15 to study the effects of parents' educational expectations and children's educational expectations on children's cognition and depression. The results show that both parents' educational expectations and children's educational expectations have a positive impact on children's cognition. Parents' educational expectations and children's educational expectations have negative effects on children's depression. When parents' educational expectations are greater than their children's educational expectations, educational expectations have a negative impact on children's cognition and a positive impact on children's depression. In both urban and rural samples, parents' educational expectations and children's educational expectations have a positive impact on children's cognition and a negative impact on children's depression. However, the impact of educational expectations on children's cognition and depression was greater in rural areas than in urban areas. When parents' educational expectations are greater than their children's educational expectations, educational expectations in urban areas have no effect on children's cognition.

Vocational Identity Status in Chinese Emerging Adults with and without Hearing Impairment: Latent Profiles and Relationships with Self-Esteem and Subjective Well-Being.

This study aimed to (1) explore the configuration of vocational identity status among emerging adults with and without hearing impairment using latent profile analysis, and (2) investigate the relationships between vocational identity status and self-esteem and subjective well-being. In total, 408 students without disabilities and 432 with hearing impairments from two Chinese higher institutions participated in the study. The Vocational Identity Status Assessment, Rosenberg Self-Esteem scale, Satisfaction with Life Scale, and Positive and Negative Affect were used to assess the major variables. The results derived five latent profiles (achieved, foreclosed, searching moratorium, undifferentiated, and diffused) of vocational identity in the present sample. The students were over-represented in undifferentiated profiles and under-represented in achieved and foreclosed ones. Hearing impairment significantly affected vocational identity status profile membership. The results showed that emerging adults with achievement and foreclosure statuses displayed healthy psychological outcomes, having the highest self-esteem, life satisfaction, and positive affect, and the lowest negative affect. In contrast, the diffused group showed the most disturbing pattern with the lowest self-esteem, life satisfaction, and positive affect, and the highest negative affect. The research findings reveal some notable issues in vocational identity status for emerging Chinese adults, raising concerns about the influence of hearing impairment on vocational identity formation, and provide implications for Chinese society to facilitate college students' career development process to promote their vocational identity status and enhance their self-esteem and subjective well-being.

Comparative transcriptomics reveals the immune dynamics during the molting cycle of swimming crab Portunus trituberculatus.

Molting is one of the most important biological processes of crustacean species, and a number of molecular mechanisms facilitate this complex procedure. However, the understanding of the immune mechanisms underlying crustacean molting cycle remains very limited. This study performed transcriptome sequencing in hemolymph and hepatopancreas of the swimming crab (Portunus trituberculatus) during the four molting stages: post-molt (AB), inter-molt (C), pre-molt (D), and ecdysis (E). The results showed that there were 78,572 unigenes that were obtained in the hemolymph and hepatopancreas of P. trituberculatus. Further analysis showed that 98 DEGs were involved in immunity response of hemolymph and hepatopancreas, and most of the DEGs participated in the process of signal transduction, pattern recognition proteins/receptors, and antioxidative enzymes system. Specifically, the key genes and pathway involved in signal transduction including the GPCR126, beta-integrin, integrin, three genes in mitogen-activated protein kinase (MAPK) signaling cascade (MAPKKK10, MAPKK4, and p38 MAPK), and four genes in Toll pathway (Toll-like receptor, cactus, pelle-like kinase, and NFIL3). For the pattern recognition proteins/receptors, the lowest expression level of 11 genes was found in the E stage, including C-type lectin receptor, C-type lectin domain family 6 member A and SRB3/C in the hemolymph, and hepatopancreatic lectin 4, C-type lectin, SRB, Down syndrome cell adhesion molecule homolog, Down syndrome cell adhesion molecule isoform, and A2M. Moreover, the expression level of copper/zinc superoxide dismutase isoform 4, glutathione peroxidase, glutathione S-transferase, peroxiredoxin, peroxiredoxin 6, and dual oxidase 2 in stage C or stage D significantly higher than that of stage E or stage AB. These results fill in the gap of the continuous transcriptional changes that are evident during the molting cycle of crab and further provided valuable information for elucidating the molecular mechanisms of immune regulation during the molting cycle of crab.

Identification of diagnostic genes for both Alzheimer's disease and Metabolic syndrome by the machine learning algorithm.

Background: Alzheimer's disease is the most common neurodegenerative disease worldwide. Metabolic syndrome is the most common metabolic and endocrine disease in the elderly. Some studies have suggested a possible association between MetS and AD, but few studied genes that have a co-diagnostic role in both diseases. Methods: The microarray data of AD (GSE63060 and GSE63061 were merged after the batch effect was removed) and MetS (GSE98895) in the GEO database were downloaded. The WGCNA was used to identify the co-expression modules related to AD and MetS. RF and LASSO were used to identify the candidate genes. Machine learning XGBoost improves the diagnostic effect of hub gene in AD and MetS. The CIBERSORT algorithm was performed to assess immune cell infiltration MetS and AD samples and to investigate the relationship between biomarkers and infiltrating immune cells. The peripheral blood mononuclear cells (PBMCs) single-cell RNA (scRNA) sequencing data from patients with AD and normal individuals were visualized with the Seurat standard flow dimension reduction clustering the metabolic pathway activity changes each cell with ssGSEA. Results: The brown module was identified as the significant module with AD and MetS. GO analysis of shared genes showed that intracellular transport and establishment of localization in cell and organelle organization were enriched in the pathophysiology of AD and MetS. By using RF and Lasso learning methods, we finally obtained eight diagnostic genes, namely ARHGAP4, SNRPG, UQCRB, PSMA3, DPM1, MED6, RPL36AL and RPS27A. Their AUC were all greater than 0.7. Higher immune cell infiltrations expressions were found in the two diseases and were positively linked to the characteristic genes. The scRNA-seq datasets finally obtained seven cell clusters. Seven major cell types including CD8 T cell, monocytes, T cells, NK cell, B cells, dendritic cells and macrophages were clustered according to immune cell markers. The ssGSEA revealed that immune-related gene (SNRPG) was significantly regulated in the glycolysis-metabolic pathway. Conclusion: We identified genes with common diagnostic effects on both MetS and AD, and found genes involved in multiple metabolic pathways associated with various immune cells.

A systematic review of telehealth screening, assessment, and diagnosis of autism spectrum disorder.

There is a significant delay between parents having concerns and receiving a formal assessment and Autism Spectrum Disorder (ASD) diagnosis. Telemedicine could be an effective alternative that shortens the waiting time for parents and primary health providers in ASD screening and diagnosis. We conducted a systematic review examining the uses of telemedicine technology for ASD screening, assessment, or diagnostic purposes and to what extent sample characteristics and psychometric properties were reported. This study searched four databases from 2000 to 2022 and obtained 26 studies that met the inclusion criteria. The 17 applications used in these 26 studies were divided into three categories based on their purpose: screening, diagnostic, and assessment. The results described the data extracted, including study characteristics, applied methods, indicators seen, and psychometric properties. Among the 15 applications with psychometric properties reported, the sensitivity ranged from 0.70 to 1, and the specificity ranged from 0.38 to 1. The present study highlights the strengths and weaknesses of current telemedicine approaches and provides a basis for future research. More rigorous empirical studies with larger sample sizes are needed to understand the feasibility, strengths, and limitations of telehealth technologies for screening, assessing, and diagnosing ASD.

Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review.

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.

Identification and Validation of a Five-Gene Diagnostic Signature for Preeclampsia.

Preeclampsia is the leading cause of morbidity and mortality for mothers and newborns worldwide. Despite extensive efforts made to understand the underlying pathology of preeclampsia, there is still no clinically useful effective tool for the early diagnosis of preeclampsia. In this study, we conducted a retrospectively multicenter discover-validation study to develop and validate a novel biomarker for preeclampsia diagnosis. We identified 38 differentially expressed genes (DEGs) involved in preeclampsia in a case-control study by analyzing expression profiles in the discovery cohort. We developed a 5-mRNA signature (termed PE5-signature) to diagnose preeclampsia from 38 DEGs using recursive feature elimination with a random forest supervised classification algorithm, including ENG, KRT80, CEBPA, RDH13 and WASH9P. The PE5-signature showed high accuracy in discriminating preeclampsia from controls with a receiver operating characteristic area under the curve value (AUC) of 0.971, a sensitivity of 0.842 and a specificity of 0.950. The PE5-signature was then validated in an independent case-control study and achieved a reliable and robust predictive performance with an AUC of 0.929, a sensitivity of 0.696, and a specificity of 0.946. In summary, we have developed and validated a five-mRNA biomarker panel as a risk assessment tool to assist in the detection of preeclampsia. This gene panel has potential clinical value for early preeclampsia diagnosis and may help us better understand the precise mechanisms involved.

Comparative Transcriptome Analysis Reveals the Process of Ovarian Development and Nutrition Metabolism in Chinese Mitten Crab, Eriocheir Sinensis.

Ovarian development is a key physiological process that holds great significance in the reproduction of the Chinese mitten crab (Eriocheir sinensis), which is an economically important crab species for aquaculture. However, there is limited knowledge for the regulatory mechanisms of ovarian development. To study the molecular mechanisms of its ovarian development, transcriptome analysis was performed in the ovary and hepatopancreas of E. sinensis during ovarian stages I (oogonium proliferation), II (endogenous vitellogenesis), and III (exogenous vitellogenesis). The results showed that 5,520 and 226 genes were differentially expressed in the ovary and hepatopancreas, respectively. For KEGG enrichment analysis, the differentially expressed genes in the ovary were significantly clustered in phototransduction-fly, phagosome, and ECM-receptor interaction. Significantly enriched pathways in the hepatopancreas included fatty acid biosynthesis, fatty acid metabolism, and riboflavin metabolism. Further analysis showed that 25 genes and several pathways were mainly involved in oogenesis, including the ubiquitin-proteasome pathway, cyclic AMP-protein kinase A signaling pathway, and mitogen-activated protein kinase signaling pathway. Twenty-five candidate genes involved in vitellogenesis and endocrine regulation were identified, such as vitellogenin, vitellogenin receptor, estrogen sulfotransferase, ecdysone receptor, prostaglandin reductase 1, hematopoietic prostaglandin D synthase and juvenile hormone acid O-methyltransferase. Fifty-six genes related to nutritional metabolism were identified, such as fatty acid synthase, long-chain-fatty-acid-CoA ligase 4, 1-acyl-sn-glycerol-3-phosphate acyltransferase 4, fatty acid-binding protein, and glycerol-3-phosphate acyltransferase 1. These results highlight the genes involved in ovarian development and nutrition deposition, which enhance our understanding of the regulatory pathways and physiological processes of crustacean ovarian development.

A Novel Necroptosis-Related lncRNA Signature for Predicting Prognosis and Immune Response of Glioma.

Glioma is one of the most common intracranial malignancies that plagues people around the world. Despite current improvements in treatment, the prognosis of glioma is often unsatisfactory. Necroptosis is a form of programmed cell death. As research progresses, the role of necroptosis in tumors has gradually attracted the attention of researchers. And lncRNA is regarded as a critical role in the development of cancer. Therefore, this study is aimed at establishing a prognostic model based on necroptosis-associated lncRNAs to accurately assess the prognosis and immune response of patients with glioma. The RNA sequences of glioma patients and normal brain samples were downloaded from The Cancer Genome Atlas (TCGA) and GTEx databases, respectively. The coexpression analysis was performed to identify the necroptosis-related lncRNAs. Then, we utilized LASSO analysis following univariate Cox analysis to construct a prognostic model. Subsequently, we applied the Kaplan-Meier curve, time-dependent receiver operating characteristics (ROC), and univariate and multivariate Cox regression analyses to assess the effectiveness of this model. And the functional enrichment analyses and immune-related analyses were employed to investigate the potential biological functions. A validation set was obtained from the Chinese Glioma Genome Atlas (CGGA) database. And qRT-PCR was employed to further validate the expression levels of selected necroptosis-associated lncRNAs. Seven necroptosis-related lncRNAs (FAM13A-AS1, JMJD1C-AS1, LBX2-AS1, ZBTB20-AS4, HAR1A, SNHG14, and LINC00900) were determined to construct a prognostic model. The area under the ROC curve (AUC) was 0.871, 0.901, and 0.911 at 1, 2, and 3 years, respectively. The risk score was shown to be an important independent predictor in both univariate and multivariate Cox regression analyses. Through functional enrichment analyses, we found that the differentially expressed genes (DEGs) were mainly enriched in protein binding and signaling-related biological functions and immune-associated pathways. In conclusion, we established and validated a novel necroptosis-related lncRNA signature, which could accurately predict the overall survival of glioma patients and serve as potential therapeutic targets.

Identification of a novel prognostic signature for HCC and analysis of costimulatory molecule-related lncRNA AC099850.3.

Costimulatory molecules are involved in initiation of anti-tumor immune responses while long non-coding RNAs (lncRNAs) regulate the development of various cancers. However, the roles of lncRNA in hepatocellular carcinoma (HCC) have not been fully established. In this study, we aimed at identifying lncRNAs-related costimulatory molecules in HCC and to construct a prognostic signature for predicting the clinical outcomes for HCC patients. Data were downloaded from The Cancer Genome Atlas database for bioinformatics analyses. Costimulatory molecules were obtained from published literature. The R software, SPSS, and GraphPad Prism were used for statistical analyses. A risk model that is based on five costimulatory molecule-related lncRNAs was constructed using lasso and Cox regression analyses. Multivariate regression analysis revealed that the risk score could predict the prognostic outcomes for HCC. Samples in high- and low-risk groups exhibited significant differences in gene set enrichment and immune infiltration levels. Through colony formation and CCK8 assays, we found that AC099850.3 was strongly associated with HCC cell proliferation. We identified and validated a novel costimulatory molecule-related survival model. In addition, AC099850.3 was found to be closely associated with clinical stages and proliferation of HCC cells, making it a potential target for HCC treatment.

Comprehensive Analysis of the Differential Expression and Prognostic Value of Histone Deacetylases in Glioma.

Gliomas are the most common and aggressive malignancies of the central nervous system. Histone deacetylases (HDACs) are important targets in cancer treatment. They regulate complex cellular mechanisms that influence tumor biology and immunogenicity. However, little is known about the function of HDACs in glioma. The Oncomine, Human Protein Atlas, Gene Expression Profiling Interactive Analysis, Broad Institute Cancer Cell Line Encyclopedia, Chinese Glioma Genome Atlas, OmicShare, cBioPortal, GeneMANIA, STRING, and TIMER databases were utilized to analyze the differential expression, prognostic value, and genetic alteration of HDAC and immune cell infiltration in patients with glioma. HDAC1/2 were considerable upregulated whereas HDAC11 was significantly downregulated in cancer tissues. HDAC1/2/3/4/5/7/8/11 were significantly correlated with the clinical glioma stage. HDAC1/2/3/10 were strongly upregulated in 11 glioma cell lines. High HDCA1/3/7 and low HDAC4/5/11 mRNA levels were significantly associated with overall survival and disease-free survival in glioma. HDAC1/2/3/4/5/7/9/10/11 are potential useful biomarkers for predicting the survival of patients with glioma. The functions of HDACs and 50 neighboring genes were primarily related to transcriptional dysregulation in cancers and the Notch, cGMP-PKG, and thyroid hormone signaling pathways. HDAC expression was significantly correlated with the infiltration of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in glioma. Our study indicated that HDACs are putative precision therapy targets and prognostic biomarkers of survival in glioma patients.