PedMiner: a tool for linkage analysis-based identification of disease-associated variants using family based whole-exome sequencing data.

With the advances of next-generation sequencing technology, the field of disease research has been revolutionized. However, pinpointing the disease-causing variants from millions of revealed variants is still a tough task. Here, we have reviewed the existing linkage analysis tools and presented PedMiner, a web-based application designed to narrow down candidate variants from family based whole-exome sequencing (WES) data through linkage analysis. PedMiner integrates linkage analysis, variant annotation and prioritization in one automated pipeline. It provides graphical visualization of the linked regions along with comprehensive annotation of variants and genes within these linked regions. This efficient and comprehensive application will be helpful for the scientific community working on Mendelian inherited disorders using family based WES data.

An alternative strategy based on ultra-high-performance supercritical fluid chromatography for full monosaccharide compositional analysis of polysaccharides in Schisandra chinensis fruits.

Due to green and environment-friendly characteristics, ultra-high-performance supercritical fluid chromatography has been widely used in analytical fields in recent years, but until now few reports are available for monosaccharide compositional analysis of macromolecule polysaccharides. In this study, an ultra-high-performance supercritical fluid chromatography technology with an unusual binary modifier is used to determine the monosaccharide compositions of natural polysaccharides. Each carbohydrate herein is simultaneously labeled as 1-pheny-3-methyl-5-pyrazolone and acetyl-derivative via pre-column derivatizations aiming to increase UV absorption sensitivity and decrease water solubility. Ten common monosaccharides are fully separated and detected on ultra-high-performance supercritical fluid chromatography combined with a photo-diode array detector by systematic optimization of multiple relevant parameters, for example, column stationary phases, organic modifiers, additives, flow rates, and so on. Compared with carbon dioxide as a mobile phase, the addition of a binary modifier increases the resolution of analytes. Additionally, this method has the advantages of small consumption of organic solvent, safety, and being environmental-friendly. It has been successfully applied for full monosaccharide compositional analysis of heteropolysaccharides from Schisandra chinensis fruits. To sum up, a new alternative approach is provided for monosaccharide compositional analysis of natural polysaccharides.

Chemical Modification of Polysaccharides: A Review of Synthetic Approaches, Biological Activity and the Structure-Activity Relationship.

Natural polysaccharides are macromolecular substances with great potential owing to their wide biological activity and low toxicity. However, not all polysaccharides have significant pharmacodynamic activity; hence, appropriate chemical modification methods can be selected according to the unique structural characteristics of polysaccharides to assist in enhancing and promoting the presentation of their biological activities. This review summarizes research progress on modified polysaccharides, including common chemical modification methods, the change in biological activity following modification, and the factors affecting the biological activity of chemically modified polysaccharides. At the same time, the difficulties and challenges associated with the structural modification of natural polysaccharides are also outlined in this review. Thus, research on polysaccharide structure modification is critical for improving the development and utilization of sugar products.

Bioaccumulation and translocation of Hg and Cr by tobacco in Sichuan Province, China: understanding the influence of soil pH.

The present study investigated the bioaccumulation and translocation of mercury (Hg) and chromium (Cr) in Yunyan 87 flue-cured tobacco (Nicotiana tabacum) and assessed the influence of soil pH on the metal uptake by plant organs at the field scale. The study was conducted in 4 different regions selected from Sichuan Province, China: Guangyuan, Luzhou, Panzhihua, and Yibin. The results revealed that Hg highly contaminated Yibin soils at 0.29 mg kg-1 and by Cr at 147 mg kg-1, which is above the permissible limit. The levels of Hg in tobacco plant organs were predominantly in the order of leaves > root > stem. The overall trend for Cr contents in tobacco organs was in the order of root > leaves > stem. The results of an index of bioaccumulation (IBA) and translocation factor (TF) showed that the values observed in Panzhihua and Guangyuan tobacco leaves were generally higher, despite the low levels of soil contamination. The linear mixed model (LMM) demonstrated that the log of Hg IBA in tobacco organs was likely to decrease with soil pH increase, whereas the log of Cr IBA only decreased in the root but gradually increased in the aerial parts with soil pH increase. The total random variation in the log of metals' IBA due to regions indicated that for Hg, 33.42% of the variation was explained by regional differences, while for Cr, only 13% was accounted. The results suggested that Yibin and Luzhou need to correct the soil acidity if they are set to reduce Hg contamination in tobacco-growing soils. Guangyuan and Panzhihua need efforts to keep the soil pH on track to avoid high contamination levels, and effective measures of soil nutrients supply are required to produce high tobacco leaf quality free from heavy metal content. The findings of this study may be used to ascertain regional differences in heavy metals, particularly Hg and Cr uptake by tobacco plant organs, and to prevent the cultivation areas contamination through soil pH monitoring.

Ambient Air Pollution Is Associated With HDL (High-Density Lipoprotein) Dysfunction in Healthy Adults.

Objective- We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results- In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 µm were 62.9 µg/m3 (8.1-331.0 µg/m3). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, -4.3 to -0.3) to 5.0% (95% CI, -7.6 to -2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 µm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant's clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein. Conclusions- Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.

A homozygous FANCM frameshift pathogenic variant causes male infertility.

PURPOSE: Fanconi anemia (FA) genes play important roles in spermatogenesis. In mice, disruption of Fancm impairs male fertility and testicular integrity, but whether FANCM pathogenic variants (PV) similarly affect fertility in men is unknown. Here we characterize a Pakistani family having three infertile brothers, two manifesting oligoasthenospermia and one exhibiting azoospermia, born to first-cousin parents. A homozygous PV in FANCM (c.1946_1958del, p.P648Lfs*16) was found cosegregating with male infertility. Our objective is to validate that FANCM p.P648Lfs*16 is the PV causing infertility in this family. METHODS: Exome and Sanger sequencing were used for PV screening. DNA interstrand crosslink (ICL) sensitivity was assessed in lymphocytes from patients. A mouse model carrying a PV nearly equivalent to that in the patients (FancmΔC/ΔC) was generated, followed by functional analysis in spermatogenesis. RESULTS: The loss-of-function FANCM PV increased ICL sensitivity in lymphocytes of patients and FancmΔC/ΔC spermatogonia. Adult FancmΔC/ΔC mice showed spermatogenic failure, with germ cell loss in 50.2% of testicular tubules and round-spermatid maturation arrest in 43.5% of tubules. In addition, neither bone marrow failure nor cancer/tumor was detected in all the patients or adult FancmΔC/ΔC mice. CONCLUSION: These findings revealed male infertility to be a novel phenotype of human patients with a biallelic FANCM PV.

Correction: A homozygous FANCM frameshift pathogenic variant causes male infertility.

Hao Win, Hui Ma and Sajjad Hussain were incorrectly affiliated to 'Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX 77030 USA'. These authors should only have been affiliated to 'Hefei National Laboratory for Physical Sciences at Microscale, The First Affiliated Hospital of USTC, USTC-SJH Joint Center for Human Reproduction and Genetics, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei 230027, China'. They were also not noted as contributing equally to the paper. Both these errors have now been corrected in the PDF and HTML versions of the paper.

Lysine glycation of apolipoprotein A-I impairs its anti-inflammatory function in type 2 diabetes mellitus.

Apolipoprotein A-I (apoA-I), the major protein compontent of high-density lipoprotein (HDL), exerts many anti-atherogenic functions. This study aimed to reveal whether nonenzymatic glycation of specific sites of apoA-I impaired its anti-inflammatory effects in type 2 diabetes mellitus (T2DM). LC-MS/MS was used to analyze the specific sites and the extent of apoA-I glycation either modified by glucose in vitro or isolated from T2DM patients. Cytokine release in THP-1 monocyte-derived macrophages was tested by ELISA. Activation of NF-kappa B pathway was detected by western blot. The binding affinity of apoA-I to THP-1 cells was measured using 125I-labeled apoA-I. We identified seven specific lysine (Lys, K) residues of apoA-I (K12, K23, K40, K96, K106, K107 and K238) that were susceptible to be glycated either in vitro or in vivo. Glycation of apoA-I impaired its abilities to inhibit the release of TNF-α and IL-1ß against lipopolysaccharide (LPS) in THP-1 cells. Besides, the glycation levels of these seven K sites in apoA-I were inversely correlated with its anti-inflammatory abilities. Furthermore, glycated apoA-I had a lower affinity to THP-1 cells than native apoA-I had. We generated mutant apoA-I (K107E, M-apoA-I) with a substitution of glutamic acid (Glu, E) for lysine at the 107th site, and found that compared to wild type apoA-I (WT-apoA-I), M-apoA-I decreased its anti-inflammatory effects in THP-1 cells. We also modeled the location of these seven K residues on apoA-I which allowed us to infer the conformational alteration of glycated apoA-I and HDL. In summary, glycation of these seven K residues altered the conformation of apoA-I and consequently impaired the protective effects of apoA-I, which may partly account for the increased risk of cardiovascular disease (CVD) in diabetic subjects.

CPSS 2.0: a computational platform update for the analysis of small RNA sequencing data.

SUMMARY: Next-generation sequencing has been widely applied to understand the complexity of non-coding RNAs (ncRNAs) in the last decades. Here, we present CPSS 2.0, an updated version of CPSS 1.0 for small RNA sequencing data analysis, with the following improvements: (i) a substantial increase of supported species from 10 to 48; (ii) improved strategies applied to detect ncRNAs; (iii) more ncRNAs can be detected and profiled, such as lncRNA and circRNA; (iv) identification of differentially expressed ncRNAs among multiple samples; (v) enhanced visualization interface containing graphs and charts in detailed analysis results. The new version of CPSS is an efficient bioinformatics tool for users in non-coding RNA research. AVAILABILITY AND IMPLEMENTATION: CPSS 2.0 is implemented in PHP + Perl + R and can be freely accessed at http://114.214.166.79/cpss2.0/. CONTACT: zyuanwei@ustc.edu.cn or qshi@ustc.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Anaconda: AN automated pipeline for somatic COpy Number variation Detection and Annotation from tumor exome sequencing data.

BACKGROUND: Copy number variations (CNVs) are the main genetic structural variations in cancer genome. Detecting CNVs in genetic exome region is efficient and cost-effective in identifying cancer associated genes. Many tools had been developed accordingly and yet these tools lack of reliability because of high false negative rate, which is intrinsically caused by genome exonic bias. RESULTS: To provide an alternative option, here, we report Anaconda, a comprehensive pipeline that allows flexible integration of multiple CNV-calling methods and systematic annotation of CNVs in analyzing WES data. Just by one command, Anaconda can generate CNV detection result by up to four CNV detecting tools. Associated with comprehensive annotation analysis of genes involved in shared CNV regions, Anaconda is able to deliver a more reliable and useful report in assistance with CNV-associate cancer researches. CONCLUSION: Anaconda package and manual can be freely accessed at http://mcg.ustc.edu.cn/bsc/ANACONDA/ .

Correlation between PD-L1 expression status and efficacy of immunotherapy as second-line or later-line therapy in advanced non-small cell lung cancer patients.

OBJECTIVE: The objective of this study is to evaluate the correlation between tumor proportionality scores (TPS) and the effectiveness of immune checkpoint inhibitors (ICIs) as the second or subsequent line therapies for individuals who received diagnoses of advanced non-small cell lung cancer (NSCLC). METHODS: The retrospective analysis was conducted on the medical records of a total of 143 patients who received diagnoses of stage IIIB/IV NSCLC and were admitted to our hospital from the beginning of 2019 to the end of September 2022. The follow-up period ended on 01 January 2023. The study used Kaplan-Meier survival curves to assess the progression-free survival (PFS) and overall survival (OS) of patients. Univariate and multivariate Cox proportional risk models were used to analyze the factors associated with the PFS and OS of advanced-stage NSCLC patients who received ICIs as the second or subsequent lines. RESULTS: Patients diagnosed with NSCLC who had a TPS ≥1% and got treatment with ICIs exhibit notably elevated rates of partial response, objective response rate, disease control rate and extended PFS in comparison to NSCLC patients with a TPS of <1% (P < 0.05). NSCLC patients with TPS within 1-49% [hazard ratio (HR) = 0.372; 95% confidence interval (CI), 0.140-0.993; P = 0.048] or ≥50% (HR = 0.276; 95% CI, 0.095-0.796; P = 0.017) were significantly associated with prolonged PFS, which were conducted by multivariate Cox regression analysis. CONCLUSION: Programmed death protein-1 expression status may be predictive markers of the effectiveness of ICIs as the second or subsequent lines of therapies in advanced NSCLC are influenced by TPS.

Efficacy of immunotherapy as second-line or later-line therapy and prognostic significance of KRAS or TP53 mutations in advanced non-small cell lung cancer patients.

OBJECTIVE: In this retrospective study, we aimed to assess the relationship between mutations in the Kirsten rats sarcoma viral oncogene (KRAS )/ tumor protein p53 (TP53 ) genes and the efficacy of immune checkpoint inhibitors (ICIs) therapy as a second-line or later-line treatment for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the clinical data of 143 patients with stage IIIB/IV NSCLC who were admitted to the Cancer Hospital of Harbin Medical University between January 2019 and September 2022. Kaplan-Meier survival curve analysis was performed to analyze the survival outcomes. Univariate and multivariate Cox proportional risk models were used to analyze the factors associated with the progression-free survival (PFS) and overall survival (OS) of advanced-stage NSCLC patients who received ICIs as second-line or later-line therapy. RESULTS: NSCLC patients with KRAS or TP53 mutations treated with ICIs showed significantly higher objective response rate, disease control rate, PFS, and OS compared to NSCLC patients with wild-type KRAS / TP53 (P  < 0.05). Multivariate Cox regression analysis showed that a combined treatment regimen of ICIs plus chemotherapy was significantly associated with prolonged PFS [hazard ratio = 0.192; 95% confidence interval (CI), 0.094-0.392; P  < 0.001] and OS (hazard ratio = 0.414; 95% CI, 0.281-0.612; P  < 0.001). CONCLUSION: KRAS or TP53 mutations were associated with improved PFS of advanced NSCLC patients treated with ICIs as second-line or later-line therapy. KRAS or TP53 mutations show great potential as clinical biomarkers to predict the efficacy of ICIs therapy.

Microbial composition and diversity of the tobacco leaf phyllosphere during plant development.

Phyllosphere-associated microorganisms affect host plant's nutrients availability, its growth and ecological functions. Tobacco leaves provide a wide-area habitat for microbial life. Previous studies have mainly focused on phyllosphere microbiota at one time point of tobacco growth process, but more is unknown about dynamic changes in phyllospheric microbial composition from earlier to the late stage of plant development. In the current study, we had determined the bacterial and fungal communities succession of tobacco growth stages (i.e., seedling, squaring, and maturing) by using both 16S rRNA sequencing for bacterial and ITS sequencing for fungi. Our results demonstrated that among tobacco growth stages, the phyllospheric bacterial communities went through more distinct succession than the fungal communities did. Proteobacteria and Actinobacteria exerted the most influence in tobacco development from seedling to squaring stages. At maturing stage, Proteobacteria and Actinobacteria dominance was gradually replaced by Firmicutes and Bacteroidetes. Network analysis revealed that Proteobacteria, as the core phyllospheric microbia, played essential role in stabilizing the whole bacterial network during tobacco development, and consequently rendered it to more profound ecological functions. During tobacco development, the contents of leaf sugar, nicotine, nitrogen and potassium were significantly correlated with either bacterial or fungal communities, and these abiotic factors accounted for 39.3 and 51.5% of the total variation, respectively. We overall evinced that the development of tobacco phyllosphere is accompanied by variant dynamics of phyllospheric microbial community.

Direct acetylation for full analysis of polysaccharides in edible plants and fungi using reverse phase liquid chromatography-multiple reaction monitoring mass spectrometry.

It is vitally important to characterize polysaccharides by monosaccharide composition method. In this study, a direct acetylation strategy combined with reversed-phase liquid chromatography electrospray tandem multiple reaction monitoring mass spectrometry (RPLC-ESI-MRM-MS) was developed for simultaneous determination of 8 aldoses (Glc, Gal, Man, Ara, Xyl, Rib, Rha and Fuc), a ketose (Fru), 2 alditols (Glc-ol and Man-ol) and 2 uronic acids (GlcA and GalA) on a high-pressure resistant reversed-phase column. Employing 1-MeIm as catalyst for direct acetylation, even though no DMSO was used to inhibit the transformation of configurations, each carbohydrate still produced a single chromatographic peak in RPLC conditions due to the ɑ- and ß- isomers merged together. Except for Fru and Man, all the other 11 carbohydrates were base-line separated in a 1.7 µm CYANO column. Therefore, correction factor method is further proposed to perfectly solve co-elution problem of Fru and Man because of occurrence of a specific Q3 ion for aldoses rather than ketose. The result was verified on a 1.7 µm Fluoro-Phenyl column with a full separation of Fru and Man. Herein, the established direct acetylation as followed RPLC-ESI-MRM-MS method was successfully applied for compositional analysis of complex polysaccharides from edible plants and fungi.

The mechanism and therapy of aortic aneurysms.

Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high risk of rupture. Because of its strong concealment, it is difficult to diagnose the disease in the early stage. At present, there are no effective drugs for the treatment of aneurysms. Surgical intervention and endovascular treatment are the only therapies. Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment. To better understand aortic aneurysm, this review elaborates on the discovery history of aortic aneurysm, main classification and clinical manifestations, related molecular mechanisms, clinical cohort studies and animal models, with the ultimate goal of providing insights into the treatment of this devastating disease. The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. If not treated in time, the aortic aneurysm eventually ruptures. An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall. The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.

Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging in C. elegans.

The chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases. Here, we systematically tag chromodomain proteins with green fluorescent protein (GFP) using CRISPR/Cas9 technology in C. elegans. By combining ChIP-seq analysis and imaging, we delineate a comprehensive expression and functional map of chromodomain proteins. We then conduct a candidate-based RNAi screening and identify factors that regulate the expression and subcellular localization of the chromodomain proteins. Specifically, we reveal an H3K9me1/2 reader, CEC-5, both by in vitro biochemistry and in vivo ChIP assays. MET-2, an H3K9me1/2 writer, is required for CEC-5 association with heterochromatin. Both MET-2 and CEC-5 are required for the normal lifespan of C. elegans. Furthermore, a forward genetic screening identifies a conserved Arginine124 of CEC-5's chromodomain, which is essential for CEC-5's association with chromatin and life span regulation. Thus, our work will serve as a reference to explore chromodomain functions and regulation in C. elegans and allow potential applications in aging-related human diseases.

Gasdermin D Deficiency in Vascular Smooth Muscle Cells Ameliorates Abdominal Aortic Aneurysm Through Reducing Putrescine Synthesis.

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with significant phenotypic alterations in vascular smooth muscle cells (VSMCs). Gasdermin D (GSDMD) is a pore-forming effector of pyroptosis. In this study, the role of VSMC-specific GSDMD in the phenotypic alteration of VSMCs and AAA formation is determined. Single-cell transcriptome analyses reveal Gsdmd upregulation in aortic VSMCs in angiotensin (Ang) II-induced AAA. VSMC-specific Gsdmd deletion ameliorates Ang II-induced AAA in apolipoprotein E (ApoE)-/- mice. Using untargeted metabolomic analysis, it is found that putrescine is significantly reduced in the plasma and aortic tissues of VSMC-specific GSDMD deficient mice. High putrescine levels trigger a pro-inflammatory phenotype in VSMCs and increase susceptibility to Ang II-induced AAA formation in mice. In a population-based study, a high level of putrescine in plasma is associated with the risk of AAA (p < 2.2 × 10-16 ), consistent with the animal data. Mechanistically, GSDMD enhances endoplasmic reticulum stress-C/EBP homologous protein (CHOP) signaling, which in turn promotes the expression of ornithine decarboxylase 1 (ODC1), the enzyme responsible for increased putrescine levels. Treatment with the ODC1 inhibitor, difluoromethylornithine, reduces AAA formation in Ang II-infused ApoE-/- mice. The findings suggest that putrescine is a potential biomarker and target for AAA treatment.

Bioaccumulation and physiological changes in the fruiting body of Agaricus bisporus (Large) sing in response to cadmium.

The bioremediation of heavy metals contaminated soils with macrofungi is a new and promising approach; hence Agaricus bisporus (Large) sing has potentially shown accumulating ability to Cd contamination. This study focused on the tolerance response by A. bisporus to different contents of Cd in the closed cup and the flat stage of fruiting body development. The contents of Cd, soluble protein, sugar, low molecular weight organic acids (LMWOAs), and antioxidant activity were investigated. The bioaccumulation factor and transfer factor results revealed that Cd accumulated in the cap of A. bisporus more than that in the stipe with the highest content being 18.38 mg kg-1 dry weight at the closed cup stage under 414.28 mg kg-1 Cd stress. High Cd content stress increased soluble protein, proline, and malonaldehyde contents at both stages; while higher peroxidase, catalase, ascorbic acid peroxidase activities, and LMWOAs contents were only recorded at the closed cup stage. On the other hand, Superoxide dismutase activities and soluble sugar content showed a complex trend. Overall, these results have successfully established that A. bisporus could resort to modulating its metabolism to avoid the destructive effects of Cd stress and could successfully accumulate Cd in the soil, which is a promising prospect for the remediation of Cd-contaminated soils.

Unveiling the m6A Methylation Regulator Links between Prostate Cancer and Periodontitis by Transcriptomic Analysis.

Objective: To identify the N6-methyladenosine (m6A) methylation regulator genes linking prostate adenocarcinoma (PRAD) and periodontitis (PD). Materials and Methods: PD and TCGA-PRAD GEO datasets were downloaded and analyzed through differential expression analysis to determine the differentially expressed genes (DEGs) deregulated in both conditions. Twenty-three m6A RNA methylation-related genes were downloaded in total. The m6A-related genes that overlapped between PRAD and PD were identified as crosstalk genes. Survival analysis was performed on these genes to determine their prognostic values in the overall survival outcomes of prostate cancer. The KEGG pathways were the most significantly enriched by m6A-related crosstalk genes. We also performed lasso regression analysis and univariate survival analysis to identify the most important m6A-related crosstalk genes, and a protein-protein interaction (PPI) network was built from these genes. Results: Twenty-three m6A methylation-related regulator genes were differentially expressed and deregulated in PRAD and PD. Among these, seven (i.e., ALKBH5, FMR1, IGFBP3, RBM15B, YTHDF1, YTHDF2, and ZC3H13) were identified as m6A-related cross-talk genes. Survival analysis showed that only the FMR1 gene was a prognostic indicator for PRAD. All other genes had no significant influence on the overall survival of patients with PRAD. Lasso regression analysis and univariate survival analysis identified four m6A-related cross-talk genes (i.e., ALKBH5, IGFBP3, RBM15B, and FMR1) that influenced risk levels. A PPI network was constructed from these genes, and 183 genes from this network were significantly enriched in pathogenic Escherichia coli infection, p53 signaling pathway, nucleocytoplasmic transport, and ubiquitin-mediated proteolysis. Conclusion: Seven m6A methylation-related genes (ALKBH5, FMR1, IGFBP3, RBM15B, YTHDF1, YTHDF2, and ZC3H13) were identified as cross-talk genes between prostate cancer and PD.

Survival and risk factors among upper tract urothelial carcinoma patients after radical nephroureterectomy in Northeast China.

Objective: The study objective was to investigate the prognostic risk factors related to overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Patients were then divided into different risk groups (based on their number of prognostic risk factors), and specific postoperative treatment plans were formulated for patients in different risk groups. Methods: We retrospectively analyzed the data of 401 patients with UTUC who underwent RNU between 2010 and 2020. Univariate and multivariate Cox regression analyses were used to evaluate the associations of clinicopathological variables with prognosis among UTUC patients. Kaplan-Meier survival analysis of patients in different risk groups (based on their number of prognostic risk factors) was conducted. Results: Multivariate Cox regression analysis showed that sex (being male), LVI, pT stage (>pT2), and lack of postoperative intravesical instillation were independent risk predictors of shorter OS, CSS, RFS, and MFS (all P<0.05). Laparoscopic RNU was also associated with shorter OS, CSS, and MFS, but not with shorter RFS (P=0.068). After risk stratification, the 5-year OS, CSS, RFS, and MFS in the high-risk group were 42.3%, 46.4%, 41%, and 46%, respectively. Conclusions: Sex (being male), LVI, pT stage (>pT2), and intravesical instillation were independent predictors of OS, CSS, RFS, and MFS for UTUC. All were risk factors, except for intravesical instillation, which was a protective factor. Additionally, laparoscopic RNU was an independent risk factor for OS, CSS, and MFS. Patients in the high-risk group may benefit greatly from adjuvant or neoadjuvant chemotherapy.