Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease.

Introduction: Disulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn's disease (CD) has not been thoroughly explored. Methods: Firstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of S100A12 with AS, UC and CD. Results: In this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes (S100A12 and LILRA5) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis. Discussion: In this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.

Daily Habits in Parkinson's Disease: Validation of the Daily Habit Scale.

Objective: The objective of the study was to validate a new scale for assessing habitual behavior-the Daily Habit Scale in patients with Parkinson's disease. Background: Parkinson's disease patients are impaired in habit learning and skill acquisition. Despite repeated practice, they have difficulty developing habitual responses. Methods: One hundred seventy-nine patients (Median (Mdn) = 69 [64-76], 65 females) participated in the study. Corrected item-to-total correlations were calculated to assess the item-convergent and item discriminant validity. Confirmatory factor analysis and assessment of internal consistency were also carried out. Concurrent validity in respect to measures of anxiety and depression, apathy, impulsivity, personality, multidimensional health locus of control, and health-related quality of life was also calculated. To determine the test-retest reliability of the scale, 30 patients (Mdn = 69 [66-73], 9 females) completed a second copy of the scale 6 months after the first. Results: Twenty-nine items (76%) and 9 items (24%) of the 38-item scale, respectively, showed a very good and good convergent validity. All the items discriminated between their own factor and the other factors. The comparative fit index of 0.932 indicated an acceptable model fit of the data, whereas the root mean square error of approximation of 0.06 moderate model fit. The scale had a good internal consistency (Cronbach α = 0.792), and a moderate test-retest reliability (0.57). Females had higher scores on two factors compared to men (Factor 3: household activities and Factor 8: sleep-related activities). Conclusions: The Daily Habit Scale is a reliable and valid tool to measure daily habits in Parkinson's disease.

Substitution Mapping and Allelic Variations of the Domestication Genes from O. rufipogon and O. nivara.

BACKGROUND: Domestication from wild rice species to cultivated rice is a key milestone, which involved changes of many specific traits and the variations of the genetic systems. Among the AA-genome wild rice species, O. rufipogon and O. nivara, have many favorable genes and thought to be progenitors of O. sativa. RESULTS: In the present study, by using O. rufipogon and O. nivara as donors, the single segment substitution lines (SSSLs) have been developed in the background of the elite indica cultivar, HJX74. In the SSSLs population, 11 genes for 5 domestication traits, including tiller angle, spreading panicle, awn, seed shattering, and red pericarp, were identified and mapped on 5 chromosomes through substitution mapping. Herein, allelic variations of 7 genes were found through sequence alignment with the known genes, that is, TA7-RUF was allelic to PROG1, TA8-RUF was allelic to TIG1, SPR4-NIV was allelic to OsLG1, AN4-RUF was allelic to An-1, SH4-NIV was allelic to SH4, and both RC7-RUF and RC7-NIV were allelic to Rc. Meanwhile, 4 genes, TA11-NIV, SPR3-NIV, AN3-NIV, and AN4-NIV, were considered as the novel genes identified in these SSSLs, because of none known genes for the related domestication traits found in the chromosomal locations of them. CONCLUSION: The results indicated that the SSSLs would be precious germplasm resources for gene mining and utilization from wild rice species, and it laid the foundation for further analyses of the novel domestication genes to better understand the genetic basis in regulating the traits variation during domestication.

A hybrid deep learning model for regional O3 and NO2 concentrations prediction based on spatiotemporal dependencies in air quality monitoring network.

Short-term prediction of urban air quality is critical to pollution management and public health. However, existing studies have failed to make full use of the spatiotemporal correlations or topological relationships among air quality monitoring networks (AQMN), and hence exhibit low precision in regional prediction tasks. With this consideration, we proposed a novel deep learning-based hybrid model of Res-GCN-BiLSTM combining the residual neural network (ResNet), graph convolutional network (GCN), and bidirectional long short-term memory (BiLSTM), for predicting short-term regional NO2 and O3 concentrations. Auto-correlation analysis and cluster analysis were first utilized to reveal the inherent temporal and spatial properties respectively. They demonstrated that there existed temporal daily periodicity and spatial similarity in AQMN. Then the identified spatiotemporal properties were sufficiently leveraged, and monitoring network topological information, as well as auxiliary pollutants and meteorology were also adaptively integrated into the model. The hourly observed data from 51 air quality monitoring stations and meteorological data in Shanghai were employed to evaluate it. Results show that the Res-GCN-BiLSTM model was better adapted to the pollutant characteristics and improved the prediction accuracy, with nearly 11% and 17% improvements in mean absolute error for NO2 and O3, respectively compared to the best performing baseline model. Among the three types of monitoring stations, traffic monitoring stations performed the best for O3, but the worst for NO2, mainly due to the impacts of intensive traffic emissions and the titration reaction. These findings illustrate that the hybrid architecture is more suitable for regional pollutant concentration.

Development and Validation of a Daily Habit Scale.

Habits are defined as automatic behaviours triggered by cues and performed without awareness. They are difficult to control and mentally efficient, which contrasts with goal-directed behaviour, which is characterised by active thought, high computational effort, and the ability to modify this behaviour in response to a changing environment and contextual demands. Habits are not only defined by the frequency with which a behaviour is performed but represent a complex construct that also includes the strength and automaticity of the habitual behaviour. We report here the development and validation of a Daily Habit Scale (DHS) to assess the frequency, automaticity, and strength of daily habits in healthy individuals. Item reduction based on factor analysis resulted in a scale with 38 items grouped into eight factors explaining 52.91% of the variance. The DHS showed very good internal consistency (Cronbach alpha = 0.738) and test-retest reliability (Intraclass correlation coefficient = 0.892, p<0.001) as well as convergent and divergent reliability compared to other scales measuring habits. We found a significant effect of age, gender, anxiety, and depression on the DHS. Considering certain limitations of the DHS, such as not considering the context of performance of habits, and the absence of certain items, such as transportation use, the results of this study suggest that DHS is a reliable and valid measure of daily habits that can be used by both clinicians and researchers as a measure of daily habits.

FtUGT79A15 is responsible for rutinosylation in flavonoid diglycoside biosynthesis in Fagopyrum tataricum.

Tartary buckwheat shows health benefits with its high antioxidant activity and abundant flavonoid content. However, glycosylated flavonoid accumulation patterns and their molecular basis remain unidentified in Tartary buckwheat. Here, our metabolomics analysis revealed that F3'H branching was the major flavonoid metabolic flux in Tartary buckwheat. Interestingly, metabolome results also showed that the most abundant flavonoids were mainly in the glycosylated form, including flavonoid glycosides and flavonoid diglycosides in Tartary buckwheat. However, the flavonoid glycosides glycosyltransferase (GGT) gene catalyzing the second glycosylation step of flavonoid diglycoside has not been discovered yet in Tartary buckwheat. Thus, we explored GGT genes in the transcriptome-metabolome correlation network and confirmed that FtUGT79A15 showed the rhamnosyltransferase activity to catalyze quercetin 3-O-glucoside to rutin invitro and inplanta. Overall, FtUGT79A15 was identified to involve in the flavonoid diglycoside biosynthesis pathway in Tartary buckwheat.

Multidisciplinary management for Peutz-Jeghers syndrome and prevention of vertical transmission to offspring using preimplantation genetic testing.

BACKGROUND: Peutz Jeghers syndrome (PJS) is an autosomal dominant genetic disorder caused by STK11 mutation with a predisposition to gastrointestinal polyposis and cancer. PJS patients suffer poor quality of life and are highly concerned about whether deleterious mutations transmit to their offspring. Therefore, this study aimed to propose feasible clinical management and provide effective preimplantation genetic testing for monogenic defect (PGT-M) strategies to protect offspring from inheriting the disease. METHODS: A hospital-based clinical retrospective analysis reviewing the clinical characteristics and fertility aspects was first conducted on 51 PJS patients at the First Affiliated Hospital of Zhengzhou University between January 2016 and March 2021. Among the 51 patients, the PGT-M strategy was further carried out in 4 couples, which started with a biopsy of the trophectoderm cells of embryos and whole genome amplification using multiple displacement amplification. Thereafter, single nucleotide polymorphism linkage analyses based on karyomapping were performed with copy number variations of the embryos identified simultaneously. Finally, prenatal diagnosis was used to verify the validity of the PGT-M results. RESULTS: A comprehensive management flowchart adopted by the multidisciplinary team model was formulated mainly focusing on clinical genetic and gastrointestinal aspects. Under the guidelines of this management, 32 embryos from 4 PJS pedigrees were diagnosed and 2 couples successfully conceived healthy babies free of the STK11 pathogenic mutation. CONCLUSIONS: Our comprehensive management could help affected families avoid having children with PJS through preimplantation genetic testing and provide meaningful guidance for multidisciplinary clinical practice on PJS.

Circular RNA MTO1 inhibits gastric cancer progression by elevating PAWR via sponging miR-199a-3p.

The effect of circular RNA MTO1 (circMTO1) signaling on the expression of miR-199a-3p in gastric carcinoma cells, and its effect on proliferation and apoptosis of gastric cancer cells were investigated in this study. RT-qPCR was performed to detect the expression levels of circMTO1 and miR-199a-3p in the cell lines and tissues of gastric cancer. The effect of circMTO1 and miR-199a-3p on the growth and apoptosis of tumor cells was detected by BrdU incorporation and Annexin V/PI staining. Target gene prediction and screening, and luciferase reporter assays were performed to validate downstream interested genes of circMTO1 and miR-199a-3p. The expression levels of miR-199a-3p target gene PAWR (named as PRKC apoptosis WT1 Regulator Protein) was measured by RT-qPCR and Western blotting. Tumor changes in mice were detected by transfecting circMTO1. The expression of circMTO1 was significantly downregulated in the cell lines and tissues of gastric cancer, and low expression levels of circMTO1 were closely associated with poor prognosis. Overexpression of circMTO1 inhibited tumor growth, enhanced apoptosis rate and decreased cell invasion and migration. There was a significant negative relationship between the expression levels of circMTO1 and miR-199a-3p in gastric cancer tissues. Inhibiting miR-199a-3p expression or overexpression of PAWR could decrease the promotive effects of knockdown of circMTO1 on the progression of gastric cancer, and a positive relationship was established between the expression of circMTO1 and PAWR. circMTO1 can regulate the growth of gastric cancer cells by regulating miR-199a-3p/PAWR axis, thus inhibiting the development and progression of gastric cancer. Abbreviation GC: Gastric cancer; circ RNA: Circular RNA; MTO1: mitochondrial translation optimized 1 homolog.

Reactive oxygen species-responsive dexamethasone-loaded nanoparticles for targeted treatment of rheumatoid arthritis via suppressing the iRhom2/TNF-α/BAFF signaling pathway.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that results in synovitis, cartilage destruction, and even loss of joint function. The frequent and long-term administration of anti-rheumatic drugs often leads to obvious adverse effects and patient non-compliance. Therefore, to specifically deliver dexamethasone (Dex) to inflamed joints and reduce the administration frequency of Dex, we developed Dex-loaded reactive oxygen species (ROS)-responsive nanoparticles (Dex/Oxi-αCD NPs) and folic acid (FA) modified Dex/Oxi-αCD NPs (Dex/FA-Oxi-αCD NPs) and validated their anti-inflammatory effect in vitro and in vivo. In vitro study demonstrated that these NPs can be effectively internalized by activated macrophages and the released Dex from NPs significantly downregulated the expression of iRhom2, TNF-α, and BAFF in activated Raw264.7. In vivo experiments revealed that Dex/Oxi-αCD NPs, especially Dex/FA-Oxi-αCD NPs significantly accumulated at inflamed joints in collagen-induced arthritis (CIA) mice and alleviated the joint swelling and cartilage destruction. Importantly, the expression of iRhom2, TNF-α, and BAFF in the joint was inhibited by intravenous injection of Dex/Oxi-αCD NPs and Dex/FA-Oxi-αCD NPs. Collectively, our data revealed that Dex-loaded ROS-responsive NPs can target inflamed joints and attenuate arthritis, and the 'iRhom2-TNF-α-BAFF' pathway plays an important role in the treatment of RA with the NPs, suggesting that this pathway may be a novel target for RA therapy.

Anti-inflammatory and anti-apoptosis activity of taraxasterol in ulcerative colitis in vitro and in vivo.

Ulcerative colitis is closely associated with colorectal cancer, the long-standing chronic inflammation being the key etiology of ulcerative colitis. The aim of the present study was to identify the anti-inflammatory and anti-apoptosis activity of taraxasterol in ulcerative colitis. MTT assay was used to obtain the optimal concentrations of lipopolysaccharide (LPS) and taraxasterol for cell treatments in vitro. A mouse model of colitis was established via dextran sodium sulphate (DSS) administration. Levels of IL-6 and TNF-α were detected through ELISA. Flow cytometry and western blotting were used to detect apoptosis and related protein expression levels, respectively. Hematoxylin and eosin staining was performed to detect the pathological damage. The results from the MTT assay identified the optimal concentration of LPS and taraxasterol, and ELISA results demonstrated that taraxasterol treatment decreased the expression levels of IL-6 and TNF-α in vitro and in vivo, in a dose-dependent manner. Taraxasterol treatment inhibited apoptosis, and reduced the protein levels of p53, Bcl-2 associated X (BAX) and caspase-3. Finally, pathological damages were reduced in colonic tissues of mice treated with taraxasterol. Taken together, taraxasterol treatment markedly inhibited inflammation and apoptosis in ulcerative colitis. Therefore, taraxasterol may be a promising agent for decreasing the inflammatory response in ulcerative colitis and other inflammation-related diseases.

LncRNA GAS8-AS inhibits colorectal cancer (CRC) cell proliferation by downregulating lncRNA AFAP1-AS1.

LncRNA GAS8-AS1 inhibits thyroid carcinoma, while its role in colorectal cancer (CRC) is unknown. In the present study we found that plasma GAS8-AS1 was upregulated in early stage CRC patients, and downregulation of GAS8-AS1 effectively distinguished CRC patients from healthy controls. LncRNA AFAP1-AS1 was upregulated in CRC patients and was inversely correlated with GAS8-AS1 only in CRC patients but not in healthy controls. GAS8-AS1 overexpression mediated the downregulation of AFAP1-AS1 in colon cancer cells, while AFAP1-AS1 overexpression did not significantly affect GAS8-AS1 expression. Expression level of GAS8-AS1 decreased, while expression level of AFAP1-AS1 increased with the increase of primary tumor diameters. GAS8-AS1 overexpression led to inhibited, while AFAP1-AS1 overexpression led to promoted proliferation of CRC cells, and AFAP1-AS1 overexpression reduced the inhibitory effects of GAS8-AS1 overexpression on cancer cell proliferation. Therefore, GAS8-AS may inhibit CRC cell proliferation by downregulating AFAP1-AS1.

Functions of RNA N6-methyladenosine modification in cancer progression.

N6-methyladenosine (m6A) serves as a major RNA methylation modification and impacts the initiation and progression of various human cancers through diverse mechanisms. It has been reported that m6A RNA methylation is involved in different physiological and pathological processes, including stem cell differentiation and motility, immune response, cellular stress, tissue renewal and viral infection. In this review, the m6A modification and its regulatory functions in a few major cancers is introduced. The detection approaches for the m6A sites identification are discussed. Additionally, the potential of the RNA m6A modification in clinical application is discussed.

Functions of RNA N6-methyladenosine modification in cancer progression.

N6-methyladenosine (m6A) serves as a major RNA methylation modification and impacts the initiation and progression of various human cancers through diverse mechanisms. It has been reported that m6A RNA methylation is involved in different physiological and pathological processes, including stem cell differentiation and motility, immune response, cellular stress, tissue renewal and viral infection. In this review, the m6A modification and its regulatory functions in a few major cancers is introduced. The detection approaches for the m6A sites identification are discussed. Additionally, the potential of the RNA m6A modification in clinical application is discussed.

Identification and analysis of key genes associated with ulcerative colitis based on DNA microarray data.

This study aimed to identify genes that may play a role in development of ulcerative colitis (UC) and gain insight into its pathogenesis.Gene expression profiling data, including samples collected from 13 early-stage UC (EUC), 8 advanced-stage UC (AUC), and 5 control subjects, were downloaded from the Gene Expression Omnibus database under the accession number of GSE9452. Differentially expressed genes (DEGs) were identified in EUC and AUC compared with controls. DEGs for EUC and AUC, as well as AUC-specific DEGs were subjected to pathway enrichment analysis. Random Walk with Restart (RWR) was used to identify DEGs that are critical in UC based on a protein-to-protein interaction (PPI) network and the inflammatory bowel disease (IBD) pathway downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. IL17 and transforming growth factor beta TGF-ß) expression levels in colonic tissue from patients with UC and normal colonic mucosa from healthy adults were analyzed by immunohistochemistry (IHC).A total of 3511 and 911 DEGs were identified in AUC and EUC, respectively. The overlapping DEGs and the AUC-specific DEGs were both enriched in pathways related to immunity, such as antigen processing and presentation. AUC-specific DEGs were related to cell migration, such as ECM-receptor interaction. Following DEG prioritization, TLR4 and STAT1 were linked with EUC, AUC, and CD. The upregulated gene TGFB increased the number of Th17 cells, as verified by IHC. Furthermore, PIK3R1, CREBBP, and STAT1 were part of high-degree nodes in the PPI sub-network.The upregulated gene TGFB may regulate IL17 expression in UC. PIK3R1 may participate in immunity and CREBBP may interact with STAT1 in the development and progression of UC.

Thalidomide combined with chemotherapy in treating elderly patients with advanced gastric cancer.

AIM: The current systemic chemotherapy brings toxicity to human body, which elder patients suffer more than young people. The effective and well-tolerated treatment methods are of great importance for elderly advanced GC patients. This paper proposed an effective way of combining thalidomide with chemotherapy to treat elderly advanced GC patients, on the purpose of improving life quality and the treatment efficacy. METHODS: In the control group, capecitabine was given with 2000 mg/m2 daily in a manner of 2 weeks on and 1 week off for elderly advanced GC patients. In the study group, thalidomide was given with 100 mg per day concurrently with chemotherapy additionally administered. RESULTS: No significant differences were observed in the major prognostic factors among 64 eligible patients between the study and control groups. The ORRs and DCRs of the treatment and control groups showed no significant difference (P > 0.05). PFS of the study and control groups were 5.3 months (95% CI 4.5-6.2) and 4.2 months (95% CI 3.4-5.1), respectively. PFS exhibited a significant difference between the two group (P = 0.03), while the overall survivals of the patients between the two groups (10.4 months vs. 9.7 months) resulted as statistically non-significant (P = 0.47). Adverse effects were minimal in the study group, only a few patients suffered the grade 3 toxicity. The rate of drowsiness, fatigue, constipation of the study group was higher than that of the control group, and the rate of anorexia was lower (P < 0.05). CONCLUSIONS: Our results demonstrated that thalidomide combined with capecitabine was mildly effective and safe for treating elderly patients with advanced GC.

Expression and immunogenicity of NY-ESO-1 in colorectal cancer.

Serum assays of NY-ESO-1 antibodies provide a guide to discriminate between patients who suffer from different types of cancer. In the present study, the expression of NY-ESO-1 was detected with the aim to identify a novel tumor antigen in colorectal cancer (CRC). Sera were obtained from 89 healthy individuals and 236 patients with CRC with stage I, II, III and IV tumors. The NY-ESO-1 autoantibody levels were determined using an enzyme-linked immunosorbent assay. The mRNA and protein expression levels of NY-ESO-1 were detected using reverse transcription-polymerase chain reaction and immunohistochemistry, respectively, in 60 CRC and paired adjacent non-tumor tissues. NY-ESO-1 antibody was detected in 40 of the 236 (16.9%) patients with CRC. The NY-ESO-1 antibody combined with carcinoembryonic antigen enhanced the sensitivity, from 52.1 to 62.7%, of the diagnosis of CRC. The frequency of antibody positivity increased with the TNM cancer stage (8.8 vs. 28.3% in stages I+II and III+IV, respectively). The mRNA and protein expression levels of NY-ESO-1 were significantly higher in CRC tissue than in adjacent non-tumor tissue. In conclusion, NY-ESO-1 is frequently expressed in CRC with the capacity of inducing a humoral immune response in CRC patients, exhibiting the potential to be a promising biomarker for CRC.

Activin A expression in esophageal carcinoma and its association with tumor aggressiveness and differentiation.

The aim of the present study was to investigate the expression of activin A in esophageal carcinoma and its association with tumor differentiation and metastasis. A total of 57 esophageal carcinoma patients and 36 controls were included in the current study. The mRNA and protein expression levels of activin A in esophageal tumors or normal esophageal tissues were determined by reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis. In addition, the association of activin A expression with esophageal carcinoma differentiation, metastasis and recurrence postoperatively was analyzed. The mRNA and protein expression levels of activin A in esophageal carcinoma were significantly higher compared with those in normal esophageal tissues (P<0.05). The expression of activin A was higher in poorly-/moderately-differentiated esophageal tumor tissues compared with that of well-differentiated or control tissues (P<0.05). Furthermore, the expression of activin A in poorly-differentiated esophageal tumor tissues was higher compared with that of moderately-differentiated tissues (P<0.05). A positive correlation was also observed between differentiation degree and activin A expression. The expression of activin A was higher in patients with lymph node metastasis compared with those without metastasis (P<0.05). The cumulative survival rate of patients with a high expression of activin A at 1, 2 and 3 years postoperatively was significantly decreased compared with that of patients with a lower expression of activin A (P<0.05); by contrast, the cumulative recurrence rate was significantly higher in patients with a lower activin A expression (P<0.05). In conclusion, abnormal expression of activin A was detected in esophageal tumor tissues, which was correlated with the tumor differentiation, metastasis, survival and recurrence. In conclusion, activin A may be used as an auxiliary index in the diagnosis and prognosis of clinical esophageal carcinoma.