Causal association of smoking, blood lipids, and bladder cancer: Insights from a multivariable and mediation mendelian randomization investigation.

We used Mendelian randomization (MR) to examine the relationship between smoking, various categories of blood lipids, and bladder cancer (BLCA). Data for this study were drawn from the genome-wide association studies of the GSCAN consortium (~1.2 million participants), a subset of the UK Biobank (~120,000 participants), and the FinnGen consortium (2,072 cases and 307,082 controls). Initially, we utilized inverse variance weighted (IVW), complementary and sensitivity analyses, multivariable MR, and meta-analysis to confirm the association between blood lipids and BLCA. We then performed mediation MR to elucidate the relationship between smoking, blood lipids, and BLCA. Our analysis identified five lipids, including triglycerides in very large HDL, cholesterol in small VLDL, free cholesterol in very large HDL, total free cholesterol, and apolipoprotein B, as having strong and inverse associations with BLCA. These lipids demonstrated no heterogeneity or pleiotropy and exhibited consistent direction and magnitude across IVW, weighted median, and MR-Egger analyses. Our mediation MR further revealed that triglycerides in very large HDL and cholesterol in small VLDL could reduce the impact of smoking on BLCA, mediating -4.3% and -4.5% of the effect, respectively. In conclusion, our study identified five lipids exhibiting a robust inverse relationship with BLCA, two of which can buffer the impact of smoking on BLCA.

UPP1 enhances bladder cancer progression and gemcitabine resistance through AKT.

UPP1, a crucial pyrimidine metabolism-related enzyme, catalyzes the reversible phosphorylation of uridine to uracil and ribose-1-phosphate. However, the effects of UPP1 in bladder cancer (BLCA) have not been elucidated. AKT, which is activated mainly through dual phosphorylation (Thr308 and Ser473), promotes tumorigenesis by phosphorylating downstream substrates. This study demonstrated that UPP1 promotes BLCA cell proliferation, migration, invasion, and gemcitabine resistance by activating the AKT signaling pathway in vitro and in vivo. Additionally, UPP1 promoted AKT activation by facilitating the binding of AKT to PDK1 and PDK2 and the recruitment of phosphatidylinositol 3,4,5-triphosphate to AKT. Moreover, the beneficial effects of UPP1 on BLCA tumorigenesis were mitigated upon UPP1 mutation with Arg94 or MK2206 treatment (AKT-specific inhibitor). AKT overexpression or SC79 (AKT-specific activator) treatment restored tumor malignancy and drug resistance. Thus, this study revealed that UPP1 is a crucial oncogene and a potential therapeutic target for BLCA and that UPP1 activates the AKT signaling pathway and enhances tumorigenesis and drug resistance to gemcitabine.

Parkin inhibits proliferation and migration of bladder cancer via ubiquitinating Catalase.

PRKN is a key gene involved in mitophagy in Parkinson's disease. However, recent studies have demonstrated that it also plays a role in the development and metastasis of several types of cancers, both in a mitophagy-dependent and mitophagy-independent manner. Despite this, the potential effects and underlying mechanisms of Parkin on bladder cancer (BLCA) remain unknown. Therefore, in this study, we investigated the expression of Parkin in various BLCA cohorts derived from human. Here we show that PRKN expression was low and that PRKN acts as a tumor suppressor by inhibiting the proliferation and migration of BLCA cells in a mitophagy-independent manner. We further identified Catalase as a binding partner and substrate of Parkin, which is an important antioxidant enzyme that regulates intracellular ROS levels during cancer progression. Our data showed that knockdown of CAT led to increased intracellular ROS levels, which suppressed cell proliferation and migration. Conversely, upregulation of Catalase decreased intracellular ROS levels, promoting cell growth and migration. Importantly, we found that Parkin upregulation partially restored these effects. Moreover, we discovered that USP30, a known Parkin substrate, could deubiquitinate and stabilize Catalase. Overall, our study reveals a novel function of Parkin and identifies a potential therapeutic target in BLCA.

USP43 stabilizes c-Myc to promote glycolysis and metastasis in bladder cancer.

A hallmark of tumor cells, including bladder cancer (BLCA) cells, is metabolic reprogramming toward aerobic glycolysis (Warburg effect). The classical oncogene MYC, which is crucial in regulating glycolysis, is amplified and activated in BLCA. However, direct targeting of the c-Myc oncoprotein, which regulates glycolytic metabolism, presents great challenges and necessitates the discovery of a more clarified regulatory mechanism to develop selective targeted therapy. In this study, a siRNA library targeting deubiquitinases identified a candidate enzyme named USP43, which may regulate glycolytic metabolism and c-Myc transcriptional activity. Further investigation using functional assays and molecular studies revealed a USP43/c-Myc positive feedback loop that contributes to the progression of BLCA. Moreover, USP43 stabilizes c-Myc by deubiquitinating c-Myc at K148 and K289 primarily through deubiquitinase activity. Additionally, upregulation of USP43 protein in BLCA increased the chance of interaction with c-Myc and interfered with FBXW7 access and degradation of c-Myc. These findings suggest that USP43 is a potential therapeutic target for indirectly targeting glycolytic metabolism and the c-Myc oncoprotein consequently enhancing the efficacy of bladder cancer treatment.

TRAIP suppresses bladder cancer progression by catalyzing K48-linked polyubiquitination of MYC.

TRAF-interacting protein (TRAIP), an E3 ligase containing a RING domain, has emerged as a significant contributor to maintaining genome integrity and is closely associated with cancer. Our study reveals that TRAIP shows reduced expression in bladder cancer (BLCA), which correlates with an unfavorable prognosis. In vitro and in vivo, TRAIP inhibits proliferation and migration of BLCA cells. MYC has been identified as a novel target for TRAIP, wherein direct interaction promotes K48-linked polyubiquitination at neighboring K428 and K430 residues, ultimately resulting in proteasome-dependent degradation and downregulation of MYC transcriptional activity. This mechanism effectively impedes the progression of BLCA. Restoring MYC expression reverses suppressed proliferation and migration of BLCA cells induced by TRAIP. Moreover, our results suggest that MYC may bind to the transcriptional start region of TRAIP, thereby exerting regulatory control over TRAIP transcription. Consequently, this interaction establishes a negative feedback loop that regulates MYC expression, preventing excessive levels. Taken together, this study reveals a mechanism that TRAIP inhibits proliferation and migration of BLCA by promoting ubiquitin-mediated degradation of MYC.

Research progress on vegetation restoration of road slopes in China.

China is the largest country in road construction due to rapid economy growth, which results in a large number of exposed slopes. Vegetation restoration of these road slopes has become the dominant method in ecological restoration. We reviewed research progress from three aspects, including key technologies for road slope vegetation restoration, application of vegetation restoration engineering, and factors influencing the vegetation restoration efforts. The slope protection technologies commonly used in road slope vegetation restoration include soil spraying technology, vegetation concrete slope protection technology, thick base material technology, and hydraulic spraying technology. In engineering applications, slope vegetation has the functions such as soil and water conservation, air purification, and landscape restoration. Currently, the most common community configuration is shrub and grass configuration. The main influencing factors of vegetation restoration on road slopes are climate, soil substrate, slope direction, plant species and community configuration used, human factors, and other natural factors (such as hydrology, altitude, microtopography, and wildlife). Future researches should focus on the mechanisms of different factors affecting road slope vegetation restoration, and study ecological substrates and slope protection technologies, plant species and diverse community configuration models suitable for road slope restoration in different climatic regions and site conditions.

Genetically supported causality between benign prostate hyperplasia and urinary bladder neoplasms: A mendelian randomization study.

Background: Observational studies have suggested a possible association between benign prostate hyperplasia (BPH) and bladder cancer (BLCA). However, these studies are prone to errors and limitations or confounding factors, making them unsuitable for assessing the causal relationship between BPH and BLCA. Objective: Two-sample Mendelian randomization (MR) was performed to determine a possible association between genetically predicted BPH and the risk of BLCA. Methods: A two-sample MR analysis was performed utilizing the Integrative Epidemiology Unit genome-wide association (GWAS) database of the Medical Research Council, United Kingdom A series of control steps, including five primary methods, were performed to identify the most suitable instrumental variables (IVs) for MR analysis. Sensitivity analysis was conducted to avoid statistical errors, including heterogeneity and pleiotropic bias. Results: Genetic variants associated with BPH (P < 5 × 10-8) and BLCA (P < 5 × 10-6) were identified as instrumental variables and assessed using GWAS summary data (BPH, 4,670 cases vs. 458,340 controls; BLCA, 1,279 cases vs. 372,016 controls). BPH exhibited a positive effect on the occurrence of BLCA (inverse variance weighted (IVW), odds ratio (OR) = 1.095, 95% confidence interval (CI) = 1.030-1.165, p = 0.003), but there was no causal effect for BLCA on BPH (IVW, OR = 1.092, 95% CI = 0.814-1.465, p = 0.554). Conclusion: Genetically predicted BPH was associated with a higher risk of BLCA in all histological subtypes. In contrast, the evidence was not significant to back the causality of genetically induced BLCA on BPH. These findings indicate that BPH plays a key role in developing BLCA in the European population. Further studies are needed to uncover the underlying mechanisms.

MYBL2 promotes proliferation and metastasis of bladder cancer through transactivation of CDCA3.

The transcription factor MYB proto-oncogene like 2 (MYBL2) is critical in regulating gene expression and tumorigenesis. However, the biological function of MYBL2 in bladder cancer (BLCA) remains to be elucidated. Here, we first revealed that MYBL2 was elevated in BLCA tissues and significantly correlated with clinicopathological parameters and cancer-specific survival in BLCA patients. Phenotypic assays showed that MYBL2 deficiency suppressed the proliferation and migration of BLCA cells in vitro and in vivo, whereas MYBL2 overexpression contributed to the opposite phenotype. Mechanistically, MYBL2 could bind to the promoter of its downstream target gene cell division cycle-associated protein 3 (CDCA3) and transactivate it, which in turn promoted the malignant phenotype of BLCA cells. Further investigations revealed that MYBL2 interacted with forkhead box M1 (FOXM1) to co-regulate the transcription of CDCA3. In addition, MYBL2/FOXM1 and CDCA3 might activate Wnt/ß-catenin signaling, thereby promoting the malignant phenotype of BLCA cells. In conclusion, the current study identifies MYBL2 as an oncogene in BLCA. MYBL2 can accelerate the proliferation and metastasis of BLCA through the transactivation of CDCA3.

Changes of Serum Homocysteine and Vitamin B12, but Not Folate Are Correlated With Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis of Case-Control Studies.

Background: Obsessive-compulsive disorder (OCD) a complex neuropsychiatric disorder, is characterized by irresistible obsessive thinking and compulsive behavior. Folate is a member of water-soluble vitamins in the human body and sustains many normal daily activities (e.g., exercise, sleep, and memory). Homocysteine, a sulfur-containing non-essential amino acid, has been investigated in numerous psychiatric disorders (e.g., OCD). Vitamin B12 is a type of complex organic compound with cobalt contained. Moreover, vitamin B12 and folate deficiency and high levels of homocysteine were found to have an effect on brain functions and also lead to non-specific psychiatric symptoms. Objectives: This study aimed to confirm the epidemiological evidence of OCD and investigate whether vitamin B12, folate, and homocysteine have an effect on the etiology of OCD. Methods: A systematic search was conducted on eight databases (i.e., PubMed, Embase, Web of Science, the Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database), and the retrieval time was up to March 2021. The available articles involving patients with OCD with/without abnormal serum levels of vitamin B12, folate, and homocysteine were comprehensively reviewed and analyzed. Results: A total of 5 studies involving 309 patients were included in this meta-analysis, including 172 cases in the experimental group and 137 in the control group. The content of folate in the OCD group was not significantly different from that in the control group (SMD = -0.089, 95%CI -0.755 to 0.577, p = 0.794). And serum homocysteine was significantly higher in the patients with OCD (SMD = 1.132, 95%CI 0.486 to 1.778, p = 0.001). Vitamin B12 was significantly lower in patients with OCD (SMD = -0.583, 95%CI -0.938 to -0.229, p = 0.001). Conclusions: This meta-analysis shows serum high levels of homocysteine, low levels of vitamin B12, and normal folate level are closely correlated with OCD. However, high-quality case-control studies should be further conducted to explore the correlation between serum levels of vitamin B12, folate, homocysteine, and OCD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021262161; PROSPERO (Number CRD#42021262161).

Knowledge of Infection Prevention and Attitudes Towards HIV/AIDS Among Chinese Dental Bachelor Interns: An Appeal for Educational Intervention.

PURPOSE: The present study aimed to assess the current situation of Chinese dental bachelor interns on HIV/AIDS-related knowledge and their attitudes towards HIV/AIDS patients. MATERIALS AND METHODS: A cross-sectional, paper-based survey involving 147 dental students from three Chinese dental schools was conducted. Students were recruited to complete the questionnaire regarding their knowledge, awareness and attitudes concerning HIV/AIDS anonymously and voluntarily. RESULTS: A total of 144 students responded to the study, generating a response rate of 98.0%. Although 97.0% of the dental students believed dentists were at high risk of HIV infection, 97.2% of students expressed no prejudice towards HIV/AIDS patients and stated their willingness to provide oral healthcare service for such patients. No statistically significant differences in the responses on attitudes and some basic knowledge were found between students who had received the relevant education about infection control and the students who had not. However, regarding most questions about oral manifestations in adult and paediatric patients living with AIDS, the students who received relevant education showed more knowledge than the students who did not (p <0.05). The cognitive level about respecting HIV/AIDS patients' autonomy and privacy was generally low in all the students. CONCLUSIONS: Most of the dental students in this survey held positive attitudes towards HIV/AIDS patients and good grasp of some basic knowledge about HIV/AIDS. On the other hand, the questionnaire results reflected gaps in education, such as respecting HIV/AIDS patients' privacy.

Transcriptional downregulation of miR-127-3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5.

Prostate cancer (PCa) is one of the most common cancers in males and particularly tends to metastasize to bone. Currently, metastatic bone disease is incurable, and new therapies need to be developed. Our study aims to determine the role of miR-127-3p in PCa metastasis to bone. The results demonstrate that miR-127-3p is markedly reduced in bone metastasis-positive PCa tissues relative to that in bone metastasis-negative PCa tissues. Furthermore, overexpressing miR-127-3p inhibits PCa cell invasion and migration in vitro by targeting the proteasome ß-subunit PSMB5. Moreover, CCCTC-binding factor (CTCF) transcriptionally inhibits miR-127-3p by interacting with the miR-127-3p promoter. Collectively, this study uncovers a novel mechanism of the CTCF/miR-127-3p/PSMB5 axis in promoting PCa bone metastasis, indicating that miR-127-3p could function as a promising therapeutic target against bone metastasis.

Treatment of Complex Renal Calculi by Digital Flexible Ureterorenoscopy Combined with Single-Tract Super-Mini Percutaneous Nephrolithotomy in Prone Position: A Retrospective Cohort Study.

BACKGROUND Advances in percutaneous nephrolithotomy (PCNL) have resulted in smaller devices that cause less trauma and bleeding, while flexible ureterorenoscopy (f-URS) allows access to any calyces. These methods are often used in isolation, but used in combination they may improve treatment of complex renal calculi. This study assessed the effectiveness and complications of f-URS combined with super-mini-PCNL (SMP) to treat complex renal calculi. MATERIAL AND METHODS A retrospective cohort analysis was made of patients with unilateral complex renal stones treated between March 2013 and December 2016. Patients were grouped according to surgical procedure: SMP (SMP Group), f-URS holmium laser lithotripsy (f-URS Group), and combined SMP and f-URS (Combined Group). The postoperative complications and complete stone-free rate were analyzed and compared among the 3 groups. RESULTS A total of 140 patients with complex renal stones were included: 40 patients in the SMP Group, 55 in the f-URS Group, and 45 in the Combined Group. The complete stone-free rate 3 days after the procedure was 77.5% in the SMP Group, 78.2% in the f-URS Group, and 97.8% in the Combined Group (p=0.010). The operation time, intraoperative blood loss, and hospitalization time of the Combined Group were all significantly lower than those in the SMP Group but higher than those in the f-URS Group. The follow-up was 9 months (range, 6-12 months). There were no medium-term complications reported. CONCLUSIONS SMP combined with f-URS holmium laser lithotripsy in the prone position is an effective treatment for complex renal calculi.

Multimedia patient education to assist oral impression taking during dental treatment: A pilot study.

INTRODUCTION: Proper cooperation between patient and dentist is of great help to make a good oral impression. However, patients are frequently confused when information is given through traditional verbal description. The present study compared the effectiveness of the multimedia information delivery ways with the traditional verbal manner on patients' understanding level in oral impression taking. METHODS: The recruited 191 participating patients were randomly assigned to the control group (the verbal group) and two intervention groups (the video group and the picture group) according to the information delivery manner. After intervention, the patients' understanding degree was measured by questionnaire and performance evaluation of behavior feedback on the provided information quantitatively. Also, patients' self-assessment of satisfaction was interviewed by telephone. All data was analyzed by SPSS 14.0 software, and p≤0.05 was set as significant difference in advance. RESULTS: One-Way ANOVA and Chi-square showed there were no statistically significant differences in the mean age, gender composition, and educational level among the three groups (P>0.05). In both questionnaire assessment and performance evaluation, One-Way ANOVA followed by LSD indicate that the video group gained a higher score than the verbal group or the picture group (P<0.05). The questionnaire score in the picture group is significantly higher than in the control group (P<0.05), but no significant difference was shown between these two groups in patients' performance evaluation (P>0.05). Higher percentage of satisfaction was reported by patients in the two multimedia groups than that in the control group. DISCUSSION: Oral impression taking is a consecutive process that requires action cooperation between dentists and patients simultaneously. This particularity makes it more suitable for multimedia delivery. The delivery of tailored information using multimedia in this study was favored by most patients and could improve the degree of patient understanding of the oral impression taking procedures.

Transcriptome analysis of distinct Lindera glauca tissues revealed the differences in the unigenes related to terpenoid biosynthesis.

The Lindera glauca, an economically and ecologically important tree species, has emerged as a novel potential plant for the intensive studies of essential oil owing to its characteristic aroma and medicinal property in distinct tissues. However, the transcriptome information and molecular research on this species is still unknown to date. To reveal the formation and accumulation mechanism of essential oil in distinct L. glauca tissues, it is crucial to analyze transcriptome and to identify the full repertoire of potential unigenes involved in terpenoid biosynthesis. In this paper, the transcriptomes of the roots, sarcocarps, stems, leaves and kernels of L. glauca were analyzed for the first time by using short-read sequencing technology (Illumina). A total of 27.2GB valid reads (the average length=92.7bp) was obtained from distinct L. glauca tissues, and then assembled de novo into 264,831 unigenes by Trinity strategy (mean size=560.2bp). The resulting 98,141 unigenes (38%) of all the assembled unigenes were annotated in multiple public databases, of which 114 potential unigenes were identified to be involved in the terpenoid biosynthetic accumulation in L. glauca. Additionally, the differential expression profiles revealed 675, 697, 432, 1702 and 844 high tissue-specificity expressions of unigenes in the roots, sarcocarps, stems, leaves and kernels of L. glauca, respectively. Overall, these obtained comprehensive unigene resources will contribute to advance the research regarding the specific plant and more specifically discovery of genes participating in the terpenoid pathway and its regulation in specific tissues of the L. glauca, but also could help the understanding of the differential accumulation of secondary metabolites in distinct plant tissues.

Further study on biomass ash characteristics at elevated ashing temperatures: the evolution of K, Cl, S and the ash fusion characteristics.

Based on the ash-related problems during biomass combustion, the evolution of element S, Cl, K and chemical components and ash fusion characteristics of capsicum stalks, cotton stalks and wheat stalks ashed at 1000, 1200 and 1400 °C are further studied by XRF and XRD. Cl disappears at 815 °C in the form of HCl due to the aluminosilicate of sylvite. Above 1000 °C, inorganic S is released in the form of SO2 by the silicate of K2SO4, which is the main reason that ashing ratio decreases at high temperature. Except of the evaporation of KCl and K2SO4 aerosol which cause the release of K, Cl and S, K may be also reduced by the organic decomposition and the releases of metal K and KOH. The ash fusion characteristics of biomass are mainly dependent on the high-temperature molten material built up by quartz, potassium iron oxide and silicates.