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Background The application of RNA-seq technology has become more extensive and the number of analysis procedures available has increased over the past years. Selecting an appropriate workflow has become an important issue for researchers in the field. Methods In our study, six popular analytical procedures/pipeline were compared using four RNA-seq datasets from mouse, human, rat, and macaque, respectively. The gene expression value, fold change of gene expression, and statistical significance were evaluated to compare the similarities and differences among the six procedures. qRT-PCR was performed to validate the differentially expressed genes (DEGs) from all six procedures. Results Cufflinks - Cuffdiff demands the highest computing resources and Kallisto - Sleuth demands the least. Gene expression values, fold change, p and q values of differential expression (DE) analysis are highly correlated among procedures using HTseq for quantification. For genes with medium expression abundance, the expression values determined using the different procedures were similar. Major differences in expression values come from genes with particularly high or low expression levels. HISAT2 - StringTie - Ballgown is more sensitive to genes with low expression levels, while Kallisto - Sleuth may only be useful to evaluate genes with medium to high abundance. When the same thresholds for fold change and p value are chosen in DE analysis, StringTie - Ballgown produce the least number of DEGs, while HTseq - DESeq2 , - edgeR or - limma generally produces more DEGs. The performance of Cufflinks - Cuffdiff and Kallisto - Sleuth varies in different datasets. For DEGs with medium expression levels, the biological verification rates were similar among all procedures. Conclusion Results are highly correlated among RNA-seq analysis procedures using HTseq for quantification. Difference in gene expression values mainly come from genes with particularly high or low expression levels. Moreover, biological validation rates of DEGs from all six procedures were similar for genes with medium expression levels. Investigators can choose analytical procedures according to their available computer resources, or whether genes of high or low expression levels are of interest. If computer resources are abundant, one can utilize multiple procedures to obtain the intersection of results to get the most reliable DEGs, or to obtain a combination of results to get a more comprehensive DE profile for transcriptomes.

Venous thromboembolism (VTE) is serious in elderly patients undergoing laparoscopic radical cystectomy and bilateral pelvic lymph node dissection. We compared the results of two VTE prophylaxis protocols: dynamic D-dimer measurement in combination with ultrasonography screening in Experimental Group (EG), and conventional VTE prophylaxis in historical control group (HCG). Between January 2022 and January 2024, the elderly patients undergoing such surgeries in EG received dynamic measurement of plasma D-dimer at admission and at 1, 3, 7, and 14 days after surgery in combination with ultrasonography screening, and commensurate VTE mechanical prophylaxis measures. Between January 2019 and December 2021, elderly patients in HCG underwent conventional prophylaxis and mechanical measures. And they were observed carefully for VTE symptoms, with Doppler ultrasonography being performed only in patients with clinical suspicion for VTE. The incidence of VTE event, major postoperative complications, major bleeding rate, and evaluation of activities of daily living within 30 days postoperatively were compared. The preoperative and intraoperative parameters were similar between the two groups. In EG, dynamic D-dimer measurements revealed a distinct temporal declining pattern. In HCG, VTE was detected in five patients out of 98 patients (5/98, 4.08%); and in EG, eight patients were found to have DVT (8/109, 7.34%; = 0.04). The incidence of symptomatic VTE was significantly lower in EG than in HCG (one and five cases, respectively, 0.9% vs. 5.1%, = 0.04), and the incidence of postoperative asymptomatic VTE was higher in the EG than in the HCG (seven and 0 cases, respectively, 6.4% vs. 0%). The incidence of major complications was similar between the two groups ( = 0.61), with similar result regarding the incidence of major bleeding ( = 0.55). The average Barthel index score in EG was 81.0 points, significantly higher than 78.3 points of the HCG ( = 0.03), and the result demonstrated a faster recovery of activities of daily living in the Experimental Group. Our results demonstrated that postoperative dynamic D-dimer and ultrasonography measurement in elderly patients can better monitor the risk of VTE, identify asymptomatic thrombosis at an early stage, optimize the timing of intervention and improve clinical outcomes, without resulting in more complications or major bleeding. Elderly patients undergoing laparoscopic radical cystectomy could benefit from such strategies.

The TARDBP gene encodes TDP-43, a multifunctional DNA- and RNA-binding protein involved in many cellular processes. Mutations in TARDBP are associated with TDP-43 proteinopathies. In vivo and in vitro studies of mutants and peptides show similarities between TDP-43 and prion proteins, suggesting that TDP-43 derivatives may cause disease by spreading to neighboring neurons. Mutations in TARDBP , encoding TAR DNA-binding protein-43 (TDP-43), are associated with TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We compared wild-type TDP-43 and an ALS-associated mutant TDP-43 in vitro and in vivo . The A315T mutant enhances neurotoxicity and the formation of aberrant TDP-43 species, including protease-resistant fragments. The C terminus of TDP-43 shows sequence similarity to prion proteins. Synthetic peptides flanking residue 315 form amyloid fibrils in vitro and cause neuronal death in primary cultures. These data provide evidence for biochemical similarities between TDP-43 and prion proteins, raising the possibility that TDP-43 derivatives may cause spreading of the disease phenotype among neighboring neurons. Our work also suggests that decreasing the abundance of neurotoxic TDP-43 species, enhancing degradation or clearance of such TDP-43 derivatives and blocking the spread of the disease phenotype may have therapeutic potential for TDP-43 proteinopathies.

Background Bladder cancer displays a broad mutational spectrum and intratumor heterogeneity (ITH), which results in difference in molecular phenotypes and resistance to therapies. However, there are currently no clinically available measures to predict patient prognosis using ITH. We aimed to establish a clinically relevant biomarker by using ITH for informing predictive of outcomes. Methods We used the Bioconductor R package Maftools to efficiently and comprehensively analyze somatic variants of muscle-invasive bladder cancer (MIBC) from The Cancer Genome Atlas (TCGA). We then used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters as well as mutational subtypes. Results We observed a broad range of somatic mutations in MIBC from TCGA. MATH value was higher for the high-grade group than for the low-grade group ( p < 0.05). There was a strong correlation between higher MATH value and presence of TP53 mutations ( p = 0.008), as well as between lower MATH value and presence of FGFR3 mutations ( p = 0.006). Patients with FGFR3 mutation and low MATH value exhibit longer overall survival time than that of all BLCA patients ( p = 0.044), which was replicated in another bladder cancer database composed of 109 BLCA patients. Conclusion Measures of tumor heterogeneity may be useful biomarkers for identifying patients with bladder cancer. Low MATH value was an independent risk factor that predicted better prognosis for patients with FGFR3 mutation compared to all BLCA patients.

Purpose To investigate the causal effects of gene expression levels associated with mitochondrial DNA copy number (mtDNA-CN) on cancer survival outcomes. Methods We performed two-sample mendelian randomization (MR) analyses to evaluate the causal relationship between mtDNA-CN in peripheral blood and overall survival period of different cancer types. Additionally, colocalization analyses were performed to identify genes whose expression correlates with mtDNA-CN. Furthermore, we investigated how expression levels of these genes impact survival period in different cancers. Results Higher mtDNA-CN in peripheral blood is significantly associated with reduced survival period in gastric cancer (HR = 72.97, 95% CI 68.86 to 77.08, p  = 0.046). Colocalization analysis identified six genes, PNP , CDK10 , C7orf73 , NLRP2 , MYO15A , and OSGEP , that regulate the mtDNA-CN in stomach tissue. Among them, higher expressions of MYO15A , OSGEP , and CDK10 are significantly associated with shorter gastric cancer survival. Notably, the impact of OSGEP expression on survival was particularly significant in the ERBB2 amplified subgroup ( p  = 0.025). Enrichment analysis suggests that the risk genes impact overall survival in gastric cancer prognosis by modulating mitochondrial function and DNA copy number. Conclusion Higher mtDNA-CN in peripheral is correlated with the shorter overall survival in gastric cancer patient. Higher expression of MYO15A , OSGEP , and CDK10 is associated with shorter survival in gastric cancer patients, potentially by regulating mtDNA-CN, suggesting potential targets for future therapeutic interventions of gastric cancer.

Introduction Contactin‐6 (CNTN6), also known as NB‐3, is a neural recognition molecule and a member of the contactin subgroup of the immunoglobulin superfamily. Gene encoding CNTN6 is expressed in many regions of the neural system, including the accessory olfactory bulb (AOB) in mice. We aim to determine the effect of CNTN6 deficiency on the function of the accessory olfactory system (AOS). Methods We examined the effect of CNTN6 deficiency on the reproductive behavior of male mice through behavioral experiments such as urine sniffing and mate preference tests. Staining and electron microscopy were used to observe the gross structure and the circuitry activity of the AOS. Results Cntn6 is highly expressed in the vomeronasal organ (VNO) and the AOB, and sparsely expressed in the medial amygdala (MeA) and the medial preoptic area (MPOA), which receive direct and/or indirect projections from the AOB. Behavioral tests to examine reproductive function in mice, which is mostly controlled by the AOS, revealed that Cntn6−/− adult male mice showed less interest and reduced mating attempts toward estrous female mice in comparison with their Cntn6+/+ littermates. Although Cntn6−/− adult male mice displayed no obvious changes in the gross structure of the VNO or AOB, we observed the increased activation of granule cells in the AOB and the lower activation of neurons in the MeA and the MPOA as compared with Cntn6+/+ adult male mice. Moreover, there were an increased number of synapses between mitral cells and granule cells in the AOB of Cntn6−/− adult male mice as compared with wild‐type controls. Conclusion These results indicate that CNTN6 deficiency affects the reproductive behavior of male mice, suggesting that CNTN6 participated in normal function of the AOS and its ablation was involved in synapse formation between mitral and granule cells in the AOB, rather than affecting the gross structure of the AOS.

Introduction CNTN6 is an immunoglobulin domain‐containing cell adhesion molecule that belongs to the contactin family. It is involved in the development of the nervous system. We aim to determine the effect of Cntn6 deficiency on the allocentric navigation in mice. Methods We recorded the travel distance and escape time of wild‐type and Cntn6 mutant male and female mice in the Morris water maze task according to the protocol. Results There was hardly any Cntn6 expression in the hippocampus of postnatal day 0 (P0) mice, while obvious Cntn6 expression was present in the hippocampal CA1 region of the P7 mice. During the acquisition period of Morris water maze task (Day 1 to 4), Cntn6−/− male mice failed to shorten the escape time to reach platform on the third day, while the travel distance to platform was not significantly different. There was no significant difference in both escape time and travel distance to the platform among all female subjects. In the probe trial test (Day 5), spatial memory of the female mutant mice was mildly affected, while Cntn6−/− male mice were normal. In the spatial relearning test (Day 7 to 10), Cntn6−/− male mice showed no difference in escape time to the platform compared to the wild‐type male mice, while Cntn6 deficient female mice required shorter escape time to travel to the platform on day 7, day 8, and day 10. Conclusions Cntn6 is expressed in the developing hippocampus in mice. Cntn6 deficiency affects spatial learning and memory, indicating that Cntn6 plays a role in the development of hippocampus and affects allocentric navigation of the animals. Cntn6 is expressed in the developing hippocampus in mice. Cntn6 deficiency affects spatial learning of male mice. Cntn6 deficiency affects the spatial memory of female mice, while improves spatial relearning.

Renal cell carcinoma (RCC) is a common type of kidney cancer that lacks effective therapeutic options. Ginsenoside compound K (CK), an active metabolite of ginsenosides, has been reported to induce apoptosis in various types of cancer cells. However, the effects of CK in RCC remain to be elucidated. Thus, the aim of the present study was to investigate the antitumor effects of CK on RCC cells. The effects of CK on the proliferation, migration, invasion, cell cycle and apoptosis of RCC cell lines (Caki-1 and 768-O) were investigated using MTT, wound healing, Transwell and flow cytometry assays, respectively. Changes in the expression levels of long non-coding RNAs (lncRNAs) and proteins were measured via reverse transcription-quantitative PCR and western blotting, respectively. Transfections with testis associated oncogenic (THOR) small interfering RNA and pcDNA were performed to knock down and overexpress lncRNA THOR, respectively. It was found that CK could effectively inhibit the proliferation, migration and invasion of RCC cells. CK also induced cell cycle arrest and caspase-dependent apoptosis in RCC cells. Furthermore, the generation of reactive oxygen species and inhibition of the lncRNA THOR played important roles in the antitumour effects of CK in RCC cells. The present data revealed that CK was a potent antitumour agent against RCC.

Renal cell carcinoma (RCC) is a common type of kidney cancer that lacks effective therapeutic options. Ginsenoside compound K (CK), an active metabolite of ginsenosides, has been reported to induce apoptosis in various types of cancer cells. However, the effects of CK in RCC remain to be elucidated. Thus, the aim of the present study was to investigate the antitumor effects of CK on RCC cells. The effects of CK on the proliferation, migration, invasion, cell cycle and apoptosis of RCC cell lines (Caki-1 and 768-0) were investigated using MTT, wound healing, Transwell and flow cytometry assays, respectively. Changes in the expression levels of long non-coding RNAs (IncRNAs) and proteins were measured via reverse transcription-quantitative PCR and western blotting, respectively. Transfections with testis associated oncogenic (THOR) small interfering RNA and pcDNA were performed to knock down and overexpress IncRNA THOR, respectively. It was found that CK could effectively inhibit the proliferation, migration and invasion of RCC cells. CK also induced cell cycle arrest and caspase-dependent apoptosis in RCC cells. Furthermore, the generation of reactive oxygen species and inhibition of the IncRNA THOR played important roles in the antitumour effects of CK in RCC cells. The present data revealed that CK was a potent antitumour agent against RCC. Key words: renal cell carcinoma, ginsenoside compound K, reactive oxygen species, apoptosis, long non-coding RNA, testis associated oncogenic IncRNA