Effect of Cyclooxygenase Inhibition on P-Glycoprotein Expression and Phenytoin Level in Brain Tissue of Pilocarpine Induced Epilepsy in Rats

Background: Increased brain P-glycoprotein (P-gp) expression may play important role in resistance to antiseizure drugs. The present work aimed to overcome the drug resistance that develop due to overexpression of P-gp with subsequent increase in brain phenytoin level in epileptic rats, using either non-selective (indomethacin) or selective (celecoxib) cyclooxygenase inhibitors. Methods: Fifty-six adult male albino rats were randomly divided into seven groups. Epilepsy was induced using the lithium pilocarpine model. Rats received indomethacin (2.5 mg/kg) or celecoxib (20 mg/kg), either alone or combined with phenytoin (50 mg/kg). Seizures were evaluated using Racine score. Motor coordination was assessed using open field and rotarod tests. Phenytoin brain level was measured using High Performance Liquid Chromatography (HPLC), glutamate expression was measured using Enzyme Linked Immunosorbent Assay (ELISA), ATP Binding Cassette Subfamily B Member 1 (ABCB1) gene expression was assessed using Real Time-Polymerase Chain Reaction (RT-PCR), and immunohistochemical analysis was done for P-gp expression. Results: Phenytoin combination with either indomethacin or celecoxib had improved the Racine score, motor coordination on rotarod apparatus, and open field test results. Also, phenytoin combination with either indomethacin or celecoxib decreased brain glutamate level, ABCB1 gene and P-gp expression, and increased brain phenytoin level compared to treatment with phenytoin alone. This indicated that both P-gp inhibitors indomethacin and celecoxib, increased the level of phenytoin that reached the brain of rats. However, brain uptake of phenytoin was significantly enhanced using celecoxib rather than indomethacin (CI 95%, 17.092: 32.808, P-value Conclusion: Cyclooxygenase inhibition using either celecoxib or indomethacin resulted in downregulation of P-gp expression, with subsequent increase in brain phenytoin level in epileptic rats.

Correlation between c-erbB-2 and P-glycoprotein Expression in Esophageal Carcinoma

Objective： To investigate the correlation between c-erbB-2 and multidrug resistance （MDR） and its clinical significance, Methods： Immunohistochemistry stain was used to examine the expression of c-erbB-2 and flow cytometry was used to detect the expression of P-glycoprotein （P-gp） in samples from 46 patients with esophageal carcinoma. Results： The positive expression rate of c-erbB-2 was 26.1% （12/46） in the 46 cases of esophageal carcinoma, of which 4 cases being low expression and 8 cases mediumhigh expression. The positive expression rate of P-gp was 60.9% （28/46） in the 46 cases of esophageal carcinoma, of which 6 cases being low expression, 13 cases medium expression and 9 cases high expression. Comparing c-erbB-2 with P-gp expression in different lymph node metastasis statuses showed that there was significant difference （P〈0.01） between P-gp expressions with lymph node metastasis （31.09%±5.33%） and without lymph node metastasis （8.04%±3.03%） when c-erbB-2 expression was positive. Comparing c-erbB-2 with P-gp expression in different TNM stages of esophageal carcinoma showed that there was significant difference （P〈0.01） between P-gp expressions in HI Ⅳ stage （33.68%±5.51%）and in Ⅱ stage patients （9.30%±2.78%） when c-erbB-2 expression was positive. The tumor＇s size and differentiation degree were not related to c-erbB-2 and P-gp expression. Conclusion： The high level of P-gp expression was related to the positive expression of c-erbB-2 with the lymph node metastasis in clinical Ⅲ-Ⅳ stage patients of esophageal carcinoma, suggesting that the double positive might lead to a poor prognosis. However, when the c-erbB-2 expression was negative, the lymph node metastasis and clinical staging were not related to the P-gp expression in esophageal carcinoma patients.

Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice

AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice(6-12 wk old,18-22 g).When the tumors reached a size of 100 mm 3,the animals were treated as indicated,and the mice were randomly assigned to seven groups(n = 10 each).After ten days of treatment,blood samples were collected from mouse eyes,and serum was harvested by centrifugation.Mice were sacrificed,and the whole body,tumor,spleen and thymus were weighed immediately.The rate of tumor inhibition and organ indexes were calculated.The expression levels of serum cytokines,P-glycoprotein(P-GP) and multidrug resistance(MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay,Western blotting,and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction,respectively.RESULTS:The tumor inhibition rates in the treatment groups of Adriamycin(ADM) + Astragalus polysaccharides(APS)(50 mg/kg),ADM + APS(100 mg/kg),and ADM + APS(200 mg/kg) were significantly higher than in the ADM group(72.88% vs 60.36%,P = 0.013;73.40% vs 60.36%,P = 0.010;77.57% vs 60.36%,P = 0.001).The spleen indexes of the above groups were also significantly higher than in the ADM group(0.65 ± 0.22 vs 0.39 ± 0.17,P = 0.023;0.62 ± 0.34 vs 0.39 ± 0.17,P = 0.022;0.67 ± 0.20 vs 0.39 ± 0.17,P = 0.012),and the thymus indexes of the ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups were significantly higher than in the ADM group(0.20 ± 0.06 vs 0.13 ± 0.04,P = 0.029;0.47 ± 0.12 vs 0.13 ± 0.04,P = 0.000).APS was found to exert a synergistic antitumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD.The expression of interleukin-1α(IL-1α),IL-2,IL-6,and tumor necrosis factor-α(TNF-α) was significantly higher in the ADM + APS(50 mg/kg),ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups than in the ADM group;and IL-10 was significantly lower in the above groups than in the ADM group.APS could increase IL-1α,IL-2,IL-6,and TNF-α expression and decrease IL-10 levels.Compared with the ADM group,APS treatment at a dose of 50-200 mg/kg could downregulate MDR1 mRNA expression in a dose-dependent manner(0.48 ± 0.13 vs 4.26 ± 1.51,P = 0.000;0.36 ± 0.03 vs 4.26 ± 1.51,P = 0.000;0.21 ± 0.04 vs 4.26 ± 1.51,P = 0.000).The expression level of P-GP was significantly lower in the ADM + APS(200 mg/kg) group than in the ADM group(137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg,P = 0.023).CONCLUSION:APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice.This may be related to its ability to enhance the expression of IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.

Prognostic significance of MDR-1 P-glycoprotein expression in breast cancer

Objective： To investigate the expression of MDR-1 P-glycoprotein（MDR-1 Pgp） in breast cancer and analyze its correlation to the biological behavior and prognosis of the disease. Methods：The expression of MDR-1 Pgp was examined in 75 cases of breast cancer patients by using three different monoclonal antibodies（JSB1, C219 and C494） with S-P immunohistochemisty. These patients were followed up for 5 years, and the correlation between MDR-1 Pgp expression, survival rate and lymph metastasis was analyzed. Results： Positive detection of MDR-1 Pgp by JSB1, C219 and C494 in 75 cases of breast cancer was 86.7%, 48% and 85.3%, respectively. MDR-1 Pgp expression was not related to ages of patients （P 〉 0.05）. JSBl-detected expression of MDR-1 Pgp was related to lymph node metastasis（P〈 0.05）; while C219 and C494 were not（P 〉 0.05）. The patients with MDR-1 Pgp expression positively detected by either two of the three antibodies, had five-year survival rate that was significantly higher than those positively detected by all the three antibodies（P 〈 0.05）. Conclusion：Three antibodies should be used simultaneously to detect MDR-1 Pgp expression in breast cancer. Positive MDR-1 Pgp expression in breast cancer detected by all the three antibodies may represent a poor prognosis; while positive MDR-1 Pgp detection by JSB1 and C494 is associated with lymph metastasis.

CLINICAL SIGNIFICANCE OF P-GLYCOPROTEIN EXPRESSION IN BREAST CANCER

Objective: to study the clinical significance of P-glycoprotein (P-gp) in breast cancer. Methods: Expression of P-gp in 60 cases of breast cancer was examined by immunohistochemistry. P-gp expression and response to chemotherapy were comparatively investigated in 19 patients with metastatic breast cancer. Results: The P-gp was positive in 48.3% of the 60 cases of breast cancer. P-gp expression was not related to patients' age, menstruation status, number of axillary lymph nodes involved, clinical stage, histological type, and hormonal receptor status (P>0.05). The frequency of metastasis (62.1%) and mortality (51.7%) were higher in P-gp positive cases than in negative cases (16.1% vs 12.9%, P<0.005). The 5-year survival rate of P-gp positive cases (48.3%) was significantly lower than that of negative cases (87.1%) (P<0.05). In patients who received adjuvant chemotherapy distant metastasis occurred more frequently in the P-gp positive cases (94.7%) than in the P-gp negative cases (57.1%) (P=0.0468). More P-gp negative patients (7/9) than positive patients (1/10) were responsive to chemotherapy (P=0.0055). Conclusion: Immunohistochemical examination of P-gp expression is useful in predicting response to chemotherapy and prognosis in breast cancer patients. P-gp positivity is associated with poor prognosis.

CLINICAL SIGNIFICANCE OF P-GLYCOPROTEIN EXPRESSION IN METASTATIC BREAST CARCINOMA

Objectives: To evaluate the expression of P-glycoprotein (P-gp) and it's effect on chemotherapy response in metastatic breast carcinoma. Methods: 46 postoperative patients with metastatic breast carcinoma were enrolled. P-gp expression was detected by SABC immunohistochemical method. These patients were treated with combined chemotherapy of cyclophosphamide, pirarubicin and 5-fluorouracil for at least two cycles. The relationship between P-gp expression and chemotherapeutic response was analyzed. Results: The positive rate of P-gp expression was 56.5%, the P-gp expression in the patients with lung or liver metastasis was higher than that in patients with skin or lymph node metastasis (P=0.049). The overall response rate was 58.1% in 43 patients; the response rate (89.5%) of the P-gp negative group was higher than that (30.0%) of the P-gp positive group (P<0.01). The response rate (87.5%) in the patients with skin or lymph node metastasis was higher than that (40.7%) in the patients with lung or liver metastasis (P<0.05). In the postoperative patients who had received CAF or CMF regimen adjuvant chemotherapy previously, the response rate of metastatic diseases to chemotherapy had no significant difference (71.4% and 37.5%, respectively) (P=0.052). Conclusion: Patients with metastatic breast carcinoma had higher P-gp expression and these patients should be treated with non-MDR drugs chemotherapy.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Genome wide investigation of Hsf gene family in Phoebe bournei:identification,evolution,and expression after abiotic stresses

Heat shock transcription factors(Hsfs)have important roles during plant growth and development and responses to abiotic stresses.The identification and func-tion of Hsf genes have been thoroughly studied in various herbaceous plant species,but not woody species,especially Phoebe bournei,an endangered,unique species in China.In this study,17 members of the Hsf gene family were identi-fied from P.bournei using bioinformatic methods.Phyloge-netic analysis indicated that PbHsf genes were grouped into three subfamilies:A,B,and C.Conserved motifs,three-dimensional structure,and physicochemical properties of the PbHsf proteins were also analyzed.The structure of the PbHsf genes varied in the number of exons and introns.Pre-diction of cis-acting elements in the promoter region indi-cated that PbHsf genes are likely involved in responses to plant hormones and stresses.A collinearity analysis dem-onstrated that expansions of the PbHsf gene family mainly take place via segmental duplication.The expression levels of PbHsf genes varied across different plant tissues.On the basis of the expression profiles of five representative PbHsf genes during heat,cold,salt,and drought stress,PbHsf pro-teins seem to have multiple functions depending on the type of abiotic stress.This systematic,genome-wide investigation of PbHsf genes in P.bournei and their expression patterns provides valuable insights and information for further func-tional dissection of Hsf proteins in this endangered,unique species.

Decoding Retinoblastoma: Differential Gene Expression

Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study leverages computational tools to dissect the differential gene expression profiles in retinoblastoma. Methods: Employing an in silico approach, we analyzed gene expression data from public repositories by applying rigorous statistical models, including limma and de seq 2, for identifying differentially expressed genes DEGs. Our findings were validated through cross-referencing with independent datasets and existing literature. We further employed functional annotation and pathway analysis to elucidate the biological significance of these DEGs. Results: Our computational analysis confirmed the dysregulation of key retinoblastoma-associated genes. In comparison to normal retinal tissue, RB1 exhibited a 2.5-fold increase in expression (adjusted p Conclusions: Our analysis reinforces the critical genetic alterations known in retinoblastoma and unveils new avenues for research into the disease’s molecular basis. The discovery of chemoresistance markers and immune-related genes opens potential pathways for personalized treatment strategies. The study’s outcomes emphasize the power of in silico analyses in unraveling complex cancer genomics.

Dietary manganese supplementation inhibits abdominal fat deposition possibly by regulating gene expression and enzyme activity involved in lipid metabolism in the abdominal fat of broilers

Excessive abdominal fat deposition seriously restricts the production efficiency of broilers.Several studies found that dietary supplemental manganese(Mn)could effectively reduce the abdominal fat deposition of broilers,but the underlying mechanisms remain unclear.The present study aimed to investigate the effect of dietary supplementation with the inorganic or organic Mn on abdominal fat deposition,and enzyme activity and gene expression involved in lipid metabolism in the abdominal fat of male or female broilers.A total of 4201-d-old AA broilers(half males and half females)were randomly allotted by body weight and gender to 1 of 6 treatments with 10 replicates cages of 7 chicks per cage in a completely randomized design involving a 3(dietary Mn addition)×2(gender)factorial arrangement.Male or female broilers were fed with the Mn-unsupplemented basal diets containing 17.52 mg Mn kg^(-1)(d 1-21)and 15.62 mg Mn kg^(-1)(d 22-42)by analysis or the basal diets supplemented with 110 mg Mn kg^(-1)(d 1-21)and 80 mg Mn kg^(-1)(d 22-42)as either the Mn sulfate or the Mn proteinate with moderate chelation strength(Mn-Prot M)for 42 d.The results showed that the interaction between dietary Mn addition and gender had no impact(P>0.05)on any of the measured parameters;abdominal fat percentage of broilers was decreased(P<0.003)by Mn addition;Mn addition increased(P<0.004)adipose triglyceride lipase(ATGL)activity,while Mn-Prot M decreased(P<0.002)the fatty acid synthase(FAS)activity in the abdominal fat of broilers compared to the control;Mn addition decreased(P<0.009)diacylglycerol acyltransferase 2(DGAT2)mRNA expression level and peroxisome proliferator-activated receptor γ(PPARγ)mRNA and protein expression levels,but up-regulated(P<0.05)the ATGL mRNA and protein expression levels in the abdominal fat of broilers.It was concluded that dietary supplementation with Mn inhibited the abdominal fat deposition of broilers possibly via decreasing the expression of PPARγand DGAT2 as well as increasing the expression and activity of ATGL in the abdominal fat of broilers,and Mn-Prot M was more effective in inhibiting the FAS acitivity.

Effects of pyraclostrobin on growth,oxidative stress,and gene expression in relation to stress and ATP-binding cassette transporters in Tetrahymena thermophila

Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression related to stress and ATP-binding cassette(ABC)transporters in Tetrahymena thermophila were investigated.The result showed that the 96-h IC_(50)of PYR against T.thermophila was 17.2 mg/L.Moreover,PYR inhibited the growth of T.thermophila in concentration-or time-dependent manner.A morphological study revealed that the shape and size of T.thermophila changed,and damage of cell membrane surface was observed by scanning electron microscopy after 96 h of PYR exposure.The activities of superoxide dismutase(SOD)and catalase(CAT)increased throughout the experiment.In contrast,the glutathione(GSH)content was increased at 24 h and 48 h of exposure and decreased at 96 h.Moreover,a significant increase in malondialdehyde(MDA)level was observed in T.thermophila after96 h of exposure.Furthermore,PYR upregulated the HSP703,HSP705,GPx2,and ABAC15 gene expression in the 0.1–5-mg/L groups and downregulated the HSP704,HSP90,TGR,and ABCC52 mRNA levels at 96 h of exposure.These results suggest that PYR may exert adverse effects on T.thermophila by inducing oxidative stress and changing the gene expression related to ABC transporters and stress,which may enrich the understanding of the toxicity mechanism of PYR in aquatic organisms and provide reference data for aquatic ecological risk assessments.

Effects of antioxidant‑rich Lactiplantibacillus plantarum inoculated alfalfa silage on rumen fermentation, antioxidant and immunity status, and mammary gland gene expression in dairy goats

Background Milk synthesis in lactating animals demands high energy metabolism,which results in an increased production of reactive oxygen metabolites(ROM)causing an imbalance between oxidants and antioxidants thereby inducing oxidative stress(OS)on the animals.To mitigate OS and postpartum disorders in dairy goats and gain insight into the impact of dietary choices on redox status during lactation,a feeding trial was conducted using alfalfa silage inoculated with a high-antioxidant strain of Lactiplantibacillus plantarum.Methods Twenty-four Guanzhong dairy goats(38.1±1.20 kg)were randomly assigned to two dietary treatments:one containing silage inoculated with L.plantarum MTD/1(RSMTD-1),and the other containing silage inoculated with high antioxidant activity L.plantarum 24-7(ES24-7).Results ES24-7-inoculated silage exhibited better fermentation quality and antioxidant activity compared to RSMTD-1.The ES24-7 diet elevated the total antioxidant capacity(T-AOC),superoxide dismutase(SOD),glutathione peroxi-dase(GSH-Px),and catalase(CAT)activities in milk,serum,and feces of lactating goats(with the exception of T-AOC in milk).Additionally,the diet containing ES24-7 inoculated silage enhanced casein yield,milk free fatty acid(FFA)content,and vitamin A level in the goats’milk.Furthermore,an increase of immunoglobulin(Ig)A,IgG,IgM,inter-leukin(IL)-4,and IL-10 concentrations were observed,coupled with a reduction in IL-1β,IL-2,IL-6,interferon(IFN)-γ,and tumor necrosis factor(TNF)-αconcentrations in the serum of lactating goats fed ES24-7.Higher concentrations of total volatile fatty acid(VFA),acetate,and propionate were observed in the rumen fluid of dairy goats fed ES24-7 inoculated silage.Moreover,the diet containing ES24-7 inoculated silage significantly upregulated the expression of nuclear factor erythroid 2 like 2(NFE2L2),beta-carotene oxygenase 1(BCO1),SOD1,SOD2,SOD3,GPX2,CAT,glu-tathione-disulfide reductase(GSR),and heme oxygenase 1(HMOX1)genes in the mammary gland,while decreased the levels of NADPH oxidase 4(NOX4),TNF,and interferon gamma(IFNG).Conclusions These findings indicated that feeding L.plantarum 24-7 inoculated alfalfa silage not only improved rumen fermentation and milk quality in lactating dairy goats but also boosted their immunity and antioxidant status by modulating the expression of several genes related to antioxidant and inflammation in the mammary gland.

Genome-Wide Identification and Expression Analysis of the GSK3 Gene Family in Sunflower under Various Abiotic Stresses

Genes in the glycogen synthase kinase 3(GSK3)family are essential in regulating plant response to stressful conditions.This study employed bioinformatics to uncover the GSK3 gene family from the sunflower genome database.The expressions of GSK3 genes in different tissues and stress treatments,such as salt,drought,and cold,were assessed using transcriptome sequencing and quantitative real-time PCR(qRT-PCR).The study results revealed that the 12 GSK3 genes of sunflower,belonging to four classes(Classes I–IV),contained the GSK3 kinase domain and 11–13 exons.The majority of GSK3 genes were highly expressed in the leaf axil and flower,while their expression levels were relatively lower in the leaf.As a result of salt stress,six of the GSK3 genes(HaSK11,HaSK22,HaSK23,HaSK32,HaSK33,and HaSK41)displayed a notable increase in expression,while HaSK14 and HaSK21 experienced a significant decrease.With regard to drought stress,five of the GSK3 genes(HaSK11,HaSK13,HaSK21,HaSK22,and HaSK33)experienced a remarkable rise in expression.When exposed to cold stress,seven of the GSK3 genes(HaSK11,HaSK12,HaSK13,HaSK32,HaSK33,HaSK41,and HaSK42)showed a substantial increase,whereas HaSK21 and HaSK23 had a sharp decline.This research is of great importance in understanding the abiotic resistance mechanism of sunflowers and developing new varieties with improved stress resistance.

Molecular mechanism of hypoxia and alpha-ketoglutaric acid on collagen expression in scleral fibroblasts

AIM:To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid(α-KG)on scleral collagen expression.METHODS:Meta-analysis and clinical statistics were used to prove the changes in choroidal thickness(ChT)during myopia.The establishment of a hypoxic myopia model(HYP)for rabbit scleral fibroblasts through hypoxic culture and the effects of hypoxia andα-KG on collagen expression were demonstrated by Sirius red staining.Transcriptome analysis was used to verify the genes and pathways that hypoxia andα-KG affect collagen expression.Finally,real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)was used for reverse verification.RESULTS:Meta-analysis results aligned with clinical statistics,revealing a thinning of ChT,leading to scleral hypoxia.Sirius red staining indicated lower collagen expression in the HYP group and higher collagen expression in the HYP+α-KG group,showed that hypoxia reduced collagen expression in scleral fibroblasts,whileα-KG can elevated collagen expression under HYP conditions.Transcriptome analysis unveiled the related genes and signaling pathways of hypoxia andα-KG affect scleral collagen expression and the results were verified by RT-qPCR.CONCLUSION:The potential molecular mechanisms through which hypoxia andα-KG influencing myopia is unraveled and three novel genes TLCD4,TBC1D4,and EPHX3 are identified.These findings provide a new perspective on the prevention and treatment of myopia via regulating collagen expression.

A Facial Expression Recognition Method Integrating Uncertainty Estimation and Active Learning

The effectiveness of facial expression recognition(FER)algorithms hinges on the model’s quality and the availability of a substantial amount of labeled expression data.However,labeling large datasets demands significant human,time,and financial resources.Although active learning methods have mitigated the dependency on extensive labeled data,a cold-start problem persists in small to medium-sized expression recognition datasets.This issue arises because the initial labeled data often fails to represent the full spectrum of facial expression characteristics.This paper introduces an active learning approach that integrates uncertainty estimation,aiming to improve the precision of facial expression recognition regardless of dataset scale variations.The method is divided into two primary phases.First,the model undergoes self-supervised pre-training using contrastive learning and uncertainty estimation to bolster its feature extraction capabilities.Second,the model is fine-tuned using the prior knowledge obtained from the pre-training phase to significantly improve recognition accuracy.In the pretraining phase,the model employs contrastive learning to extract fundamental feature representations from the complete unlabeled dataset.These features are then weighted through a self-attention mechanism with rank regularization.Subsequently,data from the low-weighted set is relabeled to further refine the model’s feature extraction ability.The pre-trained model is then utilized in active learning to select and label information-rich samples more efficiently.Experimental results demonstrate that the proposed method significantly outperforms existing approaches,achieving an improvement in recognition accuracy of 5.09%and 3.82%over the best existing active learning methods,Margin,and Least Confidence methods,respectively,and a 1.61%improvement compared to the conventional segmented active learning method.

Global-local combined features to detect pain intensity from facial expression images with attention mechanism

The estimation of pain intensity is critical for medical diagnosis and treatment of patients.With the development of image monitoring technology and artificial intelligence,automatic pain assessment based on facial expression and behavioral analysis shows a potential value in clinical applications.This paper reports a framework of convolutional neural network with global and local attention mechanism(GLA-CNN)for the effective detection of pain intensity at four-level thresholds using facial expression images.GLA-CNN includes two modules,namely global attention network(GANet)and local attention network(LANet).LANet is responsible for extracting representative local patch features of faces,while GANet extracts whole facial features to compensate for the ignored correlative features between patches.In the end,the global correlational and local subtle features are fused for the final estimation of pain intensity.Experiments under the UNBC-McMaster Shoulder Pain database demonstrate that GLA-CNN outperforms other state-of-the-art methods.Additionally,a visualization analysis is conducted to present the feature map of GLA-CNN,intuitively showing that it can extract not only local pain features but also global correlative facial ones.Our study demonstrates that pain assessment based on facial expression is a non-invasive and feasible method,and can be employed as an auxiliary pain assessment tool in clinical practice.

Genome-wide identification and expression profiling of photosystem II(PsbX)gene family in upland cotton(Gossypium hirsutum L.)

Background Photosystem II(PSII)constitutes an intricate assembly of protein pigments,featuring extrinsic and intrinsic polypeptides within the photosynthetic membrane.The low-molecular-weight transmembrane protein PsbX has been identified in PSII,which is associated with the oxygen-evolving complex.The expression of PsbX gene protein is regulated by light.PsbX’s central role involves the regulation of PSII,facilitating the binding of quinone molecules to the Qb(PsbA)site,and it additionally plays a crucial role in optimizing the efficiency of photosynthesis.Despite these insights,a comprehensive understanding of the PsbX gene’s functions has remained elusive.Results In this study,we identified ten PsbX genes in Gossypium hirsutum L.The phylogenetic analysis results showed that 40 genes from nine species were classified into one clade.The resulting sequence logos exhibited substantial conservation across the N and C terminals at multiple sites among all Gossypium species.Furthermore,the ortholo-gous/paralogous,Ka/Ks ratio revealed that cotton PsbX genes subjected to positive as well as purifying selection pressure might lead to limited divergence,which resulted in the whole genome and segmental duplication.The expression patterns of GhPsbX genes exhibited variations across specific tissues,as indicated by the analysis.Moreover,the expression of GhPsbX genes could potentially be regulated in response to salt,intense light,and drought stresses.Therefore,GhPsbX genes may play a significant role in the modulation of photosynthesis under adverse abiotic conditions.Conclusion We examined the structure and function of PsbX gene family very first by using comparative genom-ics and systems biology approaches in cotton.It seems that PsbX gene family plays a vital role during the growth and development of cotton under stress conditions.Collectively,the results of this study provide basic information to unveil the molecular and physiological function of PsbX genes of cotton plants.

Expression Pattern, Interaction Network, and Functional Analysis of the Arabidopsis Botrytis Susceptible1 Interactor

E3 ubiquitin ligases are participated in numerous processes, regulating the response to biotic and abiotic stresses. Botrytis susceptible1 interactor (BOI) is a RING (Really Interesting New Gene)-type E3 ligase that mediates the ubiquitination of BOS1 (Botrytis susceptible1), a transcription factor involved in stress and pathogen responses. Although BOI is an E3 ligase, there are reports to show that BOI interacts with target proteins such as DELLAs or CONSTANS to repress gibberellin responses and flowering without the degradation of the target proteins. In this article, we utilize diversified methods to comprehensively analyze the expression pattern, interaction network and function of BOI gene. Firstly, 1800 bp upstream region of BOI gene from Arabidopsis thaliana (Arabidopsis) genome was isolated, and fused GUS reporter gene. The resulting expression cassette was introduced into wild-type Arabidopsis through Agrobacterium-mediated transformation. The result demonstrated that BOI gene was expressed predominantly in leaves, siliques, young roots, and flowering tissues, indicating that BOI gene may be involved in multiple processes in plant growth and development in Arabidopsis. Besides, eight candidate interacting proteins were obtained from the Arabidopsis cDNA library via yeast two-hybrid technology, including EXO70E2 (AT5G61010), WRKY7 (AT4G24240), WRKY11 (AT4G31550), WRKY17 (AT2G24570), UBP20 (AT4G17895), L5 (AT1G12290), SAUR9 (AT4G36110) and TCP21 (AT5G08330). Functional analysis of these candidate interacting proteins manifested that they related to multiple pathways, including biological and abiotic stress, programmed cell death, protein degradation, material metabolism and transcriptional regulation. In addition, the results of the transient assay proclaimed that BOI protein affects the protein stability of EXO70E2 and L5 through its E3 ubiquitin ligase activity. Our results provide novel clues for a better understanding of molecular mechanisms underlying BOI-mediated regulations.

Expression Recognition Method Based on Convolutional Neural Network and Capsule Neural Network

Convolutional neural networks struggle to accurately handle changes in angles and twists in the direction of images,which affects their ability to recognize patterns based on internal feature levels. In contrast, CapsNet overcomesthese limitations by vectorizing information through increased directionality and magnitude, ensuring that spatialinformation is not overlooked. Therefore, this study proposes a novel expression recognition technique calledCAPSULE-VGG, which combines the strengths of CapsNet and convolutional neural networks. By refining andintegrating features extracted by a convolutional neural network before introducing theminto CapsNet, ourmodelenhances facial recognition capabilities. Compared to traditional neural network models, our approach offersfaster training pace, improved convergence speed, and higher accuracy rates approaching stability. Experimentalresults demonstrate that our method achieves recognition rates of 74.14% for the FER2013 expression dataset and99.85% for the CK+ expression dataset. By contrasting these findings with those obtained using conventionalexpression recognition techniques and incorporating CapsNet’s advantages, we effectively address issues associatedwith convolutional neural networks while increasing expression identification accuracy.

Prediction of Lung Cancer Stage Using Tumor Gene Expression Data

Lung cancer remains a significant global health challenge and identifying lung cancer at an early stage is essential for enhancing patient outcomes. The study focuses on developing and optimizing gene expression-based models for classifying cancer types using machine learning techniques. By applying Log2 normalization to gene expression data and conducting Wilcoxon rank sum tests, the researchers employed various classifiers and Incremental Feature Selection (IFS) strategies. The study culminated in two optimized models using the XGBoost classifier, comprising 10 and 74 genes respectively. The 10-gene model, due to its simplicity, is proposed for easier clinical implementation, whereas the 74-gene model exhibited superior performance in terms of Specificity, AUC (Area Under the Curve), and Precision. These models were evaluated based on their sensitivity, AUC, and specificity, aiming to achieve high sensitivity and AUC while maintaining reasonable specificity.