Unraveling the interplay between dyskinesia and overactive bladder symptoms in Parkinson's disease: a comprehensive cohort study based on the long-term follow-up database of Parkinson's disease.

OBJECTIVES: Overactive bladder (OAB) and dyskinesia are frequent complications in patients with Parkinson's disease (PD). However, the correlation between OAB and dyskinesia has been insufficiently explored. The purpose of this study was to examine the relationship between dyskinesia, OAB, and clinical characteristics among individuals with PD. METHODS: 1338 PD patients were included in the present study. Demographic features were compared between patients with or without dyskinesia and OAB symptoms. Logistic regression was conducted on dyskinesia to screen clinically relevant factors. Overactive Bladder Symptom Score (OABSS) was further used to stratify the association between the severity of OAB and the occurrence of dyskinesia. RESULTS: This study indicates that both dyskinesia and OAB are significantly related to disease severity and cognitive status. PD patients with dyskinesia and OAB having higher UPDRS scores (p < 0.001), H-Y scores (p < 0.001), NMSQ (p < 0.001) and MoCA scores (p < 0.001), and lower MMSE scores (p < 0.001) are identified. The multivariate logistic regression confirms that disease duration (p = 0.041), LEDD (p < 0.001), UPDRSII (p < 0.001), MoCA (p = 0.024), urgency (p < 0.001), frequency (p < 0.001), and nocturia (p = 0.002) are independent risk factors for dyskinesia. Trend analysis indicates that the risk of dyskinesia significantly increases when patients exhibit moderate to severe OAB symptoms (OABSS > 5) (p < 0.001). No significant interactions were found between OABSS and age, gender, disease duration, LEDD, and NMSQ scores in different subgroups, indicating that dyskinesia is more pronounced in patients with OABSS > 5. DISCUSSION: This study provides compelling evidence supporting the strong correlation between OAB and dyskinesia in PD patients, emphasizing the presence of shared pathogenic mechanisms between these two conditions. Our findings underscore the importance of considering both OAB and dyskinesia in the clinical management of PD, investigating the intricate connections between OAB and dyskinesia could unveil valuable insights into the complex pathophysiology of PD and potentially identify novel therapeutic targets for more effective PD treatment strategies.

Hypermethylation of the ADIRF promoter regulates its expression level and is involved in NNK-induced malignant transformation of lung bronchial epithelial cells.

The carcinogenic mechanism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a well-known tobacco carcinogen, has not been fully elucidated in epigenetic studies. 5-Methylcytosine (5mC) modification plays a major role in epigenetic regulation. In this study, the 5mC level increased in both BEAS-2B human bronchial epithelium cells treated with 100 mg/L NNK for 24 h and NNK-induced malignant-transformed BEAS-2B cells (2B-NNK cells), suggesting that 5mC modification is associated with the malignant transformation mechanism of NNK. Using a combination of Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq), RNA sequencing (RNA-seq), and bioinformatics analysis of data from the Genomic Data Commons database, we found that the Adipogenesis regulatory factor (ADIRF) promoter region was abnormally hypermethylated, yielding low ADIRF mRNA expression, and that ADIRF overexpression could inhibit the proliferation, migration, and invasion of 2B-NNK cells. This finding suggests that ADIRF plays a tumor suppressor role in the NNK-induced malignant transformation of cells. Subsequently, using 5-Aza-2'-deoxycytidine (5-Aza-2'-dC) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Catalytically Dead Cas9 (dCas9 system), we verified that the demethylation of the ADIRF promoter region in 2B-NNK cells inhibited the proliferation, migration, and invasion ability of the cells and increased their apoptosis ability. These results suggest that abnormal 5mC modification of the ADIRF promoter plays a positive regulatory role in the pathogenesis of NNK-induced lung cancer. This study offers a new experimental basis for the epigenetic mechanism of NNK-induced lung cancer.

Psychromarinibacter sediminicola sp. nov., a novel moderately halophilic, metabolically diverse bacterium isolated from a solar saltern sediment, and comparison between members of family Roseobacteraceae.

Known for its species abundance and evolutionary status complexity, family Roseobacteraceae is an important subject of many studies on the discovery, identification, taxonomic status, and ecological properties of marine bacteria. This study compared and analyzed the phylogenetic, genomic, biochemical, and chemo taxonomical properties of seven species from three genera (Psychromarinibacter, Lutimaribacter, and Maritimibacter) of the family Roseobacteraceae. Moreover, a novel strain, named C21-152T was isolated from solar saltern sediment in Weihai, China. The values of 16S rRNA gene sequence similarity, the average nucleotide identity (ANI), the average amino acid identity (AAI), and the digital DNA-DNA hybridization (dDDH) between genomes of the novel strain and Psychromarinibacter halotolerans MCCC 1K03203T were 97.19, 78.49, 73.45, and 21.90%, respectively. Genome sequencing of strain C21-152T revealed a complete Sox enzyme system related to thiosulfate oxidization as well as a complete pathway for the final conversion of hydroxyproline to α-ketoglutarate. In addition, strain C21-152T was resistant to many antibiotics and had the ability to survive below 13% salinity. This strain had versatile survival strategies in saline environments including salt-in, compatible solute production and compatible solute transport. Some of its physiological features enriched and complemented the knowledge of the characteristics of the genus Psychromarinibacter. Optimum growth of strain C21-152T occurred at 37 â„ƒ, with 5-6% (w/v) NaCl and at pH 7.5. According to the results of the phenotypic, chemotaxonomic characterization, phylogenetic properties and genome analysis, strain C21-152T should represent a novel specie of the genus Psychromarinibacter, for which the name Psychromarinibacter sediminicola sp. nov. is proposed. The type strain is C21-152T (= MCCC 1H00808T = KCTC 92746T = SDUM1063002T).

LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer.

Introduction: Bladder cancer (BLCA) is a highly heterogeneous disease influenced by the tumor microenvironment, which may affect patients' response to immune checkpoint blockade therapy. Therefore, identifying molecular markers and therapeutic targets to improve treatment is essential. In this study, we aimed to investigate the prognostic significance of LRP1 in BLCA. Methods: We analyzed TCGA and IMvigor210 cohorts to investigate the relationship of LRP1 with BLCA prognosis. We utilized gene mutation analysis and enrichment to identify LRP1-associated mutated genes and biological processes. Deconvolution algorithms and single-cell analysis were used to understand the tumor-infiltrated cells and biological pathways associated with LRP1 expression. Immunohistochemistry was conducted to validate the bioinformatics analysis. Results: Our study revealed that LRP1 was an independent risk factor for overall survival in BLCA patients and was associated with clinicopathological features and FGFR3 mutation frequency. Enrichment analysis demonstrated that LRP1 was involved in extracellular matrix remodeling and tumor metabolic processes. Furthermore, the ssGSEA algorithm revealed that LRP1 was positively correlated with the activities of tumor-associated pathways. Our study also found that high LRP1 expression impaired patients' responsiveness to ICB therapy in BLCA, which was predicted by TIDE prediction and validated by IMvigor210 cohort. Immunohistochemistry confirmed the expression of LRP1 in Cancer-Associated Fibroblasts (CAFs) and macrophages in the tumor microenvironment of BLCA. Discussion: Our study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy.

Corrigendum: The epithelial to mesenchymal transition related gene calumenin is an adverse prognostic factor of bladder cancer correlated with tumor microenvironment remodeling, gene mutation, and ferroptosis.

[This corrects the article DOI: 10.3389/fonc.2021.683951.].

Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A.

BACKGROUND: Accumulating evidence indicates that circular RNAs (circRNAs) play important roles in various cancers. Hsa_circ_0008832 (circFBXO7) is a circRNA generated from the second exon of the human F-box only protein 7 (FBXO7). Mouse circFbxo7 is a circRNA generated from the second exon of mouse F-box only protein 7 (Fbxo7). The role of human circFBXO7 and mouse circFbxo7 in non-small cell lung cancer (NSCLC) has not been reported. METHODS: The expression of circFBXO7 was measured by quantitative real-time PCR. Survival analysis was performed to explore the association between the expression of circFBXO7 and the prognosis of patients with NSCLC. Lung cancer cell lines were transfected with plasmids. Cell proliferation, cell cycle, and tumorigenesis were evaluated to assess the effects of circFBXO7. Fluorescence in situ hybridization assay was used to identify the location of circFBXO7 and circFbxo7 in human and mouse lung cancer cells. Luciferase reporter assay was conducted to confirm the relationship between circFBXO7 and microRNA. RESULTS: In this study, we found that circFBXO7 was downregulated in NSCLC tissues and cell lines. NSCLC patients with high circFBXO7 expression had prolonged overall survival. Overexpression of circFBXO7 inhibited cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that circFBXO7 upregulated the expression of miR-296-3p target gene Krüppel-like factor 15 (KLF15) and KLF15 transactivated the expression of CDKN1A. CONCLUSIONS: CircFBXO7 acts as a tumor suppressor by a novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis, which may serve as a potential biomarker and therapeutic target for NSCLC.

Analyzing and mapping the research status, hotspots, and frontiers of biological wound dressings: An in-depth data-driven assessment.

Wound dressings can be applied over the wound sites to provide long-lasting wound management and improve wound healing. Biological wound dressings are superior to synthetic materials due to biodegradability and biocompatibility. These biomaterials have demonstrated huge potential in the field of wound dressings. Applying bibliometric analysis combined with results-based descriptions to characterize the research status, hotspots, and cutting-edge topics, this study is the first in-depth qualitative, quantitative, data-driven overview of biological wound dressings research in recent decades. Filtered data were used to construct co-citation, heatmaps, bi-clustering, strategy maps, and other analyses and visualization. The results show that research on biological wound dressings has progressed considerably in the last 5 years with extensive global collaboration. A clear knowledge base has been developed. Chitosan hydrogels, bacterial cellulose, active agents (silver nanoparticles, growth factors, curcumin, etc.), and electrospinning fibers stand out as research hotspots. The research frontiers include novel starting materials, precise and controlled release systems, and clinical and regenerative medicine applications. We interpreted an overview of the excavated topics and expected the findings here to provide a guide and inspire innovations for developing the next generation wound dressings.

High-risk early-stage lung adenocarcinoma patients are identified by an immune-related circadian clock gene signature.

Background: Twenty-four-hour oscillations of circadian rhythms control comprehensive biological processes in the human body. In lung adenocarcinoma (LUAD), chronic circadian rhythm disruption is positively associated with tumorigenesis. However, few studies focus on circadian clock gene signatures (CGSs) for prognosis evaluation of patients with early-stage LUAD. Methods: In this study, we aimed to construct a robust prognostic circadian rhythm-related biomarker from multiple public databases, including the Gene Expression Omnibus database and The Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to select optimal circadian clock gene pairs. Bioinformatic analyses were performed to estimate the abundance of different immune cells and immunohistochemical analyses were conducted to validate the differential proportion of tumor-infiltrating lymphocytes in different groups. Results: Results demonstrated that the CGS could accurately identify patients with early-stage LUAD at a high risk in the training dataset [hazard ratio (HR) =3.06; 95% confidence interval (CI): 2.47-3.78; P<0.001], testing dataset (HR =2.44; 95% CI: 1.74-3.43; P<0.001), and validation dataset (HR =2.09, 95% CI: 1.09-4.00; P=0.023). Bioinformatic and immunohistochemical analyses demonstrated that the abundance of tumor-infiltrating CD4+ T cells was higher in the low-CGS groups. Integration of the CGS and clinical characteristics improved the accuracy of the CGS in predicting overall survival (OS) of patients with early-stage LUAD. Conclusions: In conclusion, the CGS was an independent immune-related circadian biomarker that could identify early-stage LUAD patients with different OS.

Acute cytotoxicity test of PM2.5, NNK and BPDE in human normal bronchial epithelial cells: A comparison of a co-culture model containing macrophages and a mono-culture model.

BACKGROUND: Based on extensive research on cytotoxicity of exogenous compounds in vitro, it is essential to develop a cell model that better mimics environment in vivo to explore cytotoxic mechanisms of exogenous compounds. METHODS: A co-culture system was established using a transwell system with Beas-2B and U937 cells. Cells were treated with fine particulate matter (PM2.5; 25, 50 and 100 µg/mL), nicotine-derived nitrosamine ketone (NNK; 50, 100 and 200 µg/mL) and benzo(a)pyrene diol epoxide (BPDE; 0.5, 2 and 8 µM) for 24 h. Cell proliferation, apoptosis and cell cycle, DNA damage were detected by CCK-8 and EdU, flow cytometry, and comet assay, respectively. Differentially expressed transcript and cytokine concentrations were determined by transcriptome sequencing and Cytokine Array, respectively. RESULTS: Compared with mono-culture, cell proliferation increased, apoptosis decreased, and DNA damage decreased in a dose-response relationship in co-culture. Gene expression profile was significantly different in co-culture, with significantly increased expression levels of 48 cytokines in co-culture. CONCLUSION: Cytotoxic damage to Beas-2B cells induced by exogenous carcinogens, including PM2.5, NNK and BPDE, was significantly reduced in a co-culture system compared with a mono-culture system. The mechanism may be related to changes in expression of cytokines, such as LIF, and activation of related pathways, such as TNF signaling pathway. Cytotoxic damage to Beas-2B induced by PM2.5, NNK and BPDE, was significantly reduced in co-culture. The mechanism may be related to changes in expression of cytokines and activation of related pathways. These findings provide new insights into cytotoxicity and experimental basis for safety evaluations of exogenous carcinogens.

From macrophyte to algae: Differentiated dominant processes for internal phosphorus release induced by suspended particulate matter deposition.

In shallow lakes, eutrophication leads to a shift of the macrophyte-dominated clear state towards an algae-dominated turbid state. Phosphorus (P) is a crucial element during this shift and is usually concentrated in the suspended particulate matter (SPM) in water. However, the dominant processes controlling internal P release in the algae- (ADA) and macrophyte-dominated (MDA) areas under the influence of P-concentrated SPM remains unclear. In this study, we conducted monthly field observations of P exchange across the sediment-water interface (SWI) with the deposition of SPM in the ADA and MDA of Lake Taihu. Results revealed that both algae- and macrophyte-originated SPM led to the depletion of oxygen across the SWI during summer and autumn. Redox-sensitive P (Fe-P) and organic P (Org-P) were the dominant mobile P fractions in both areas. High fluxes of P across the SWI were observed in both areas during the summer and autumn. However, the processes controlling P release were quite different. In MDA, P release was mostly controlled by a traditional Fe-P dissolution process influenced by the coupled cycling of iron, sulfur, and P. In the ADA, Org-P control was intensified with the deterioration of algal bloom status, accompanied with the dissolution of Fe-P. Evidence from the current study revealed that the dominant process controlling the internal P release might gradually shift from Fe-P to a coupled process of Fe-P and Org-P with the shift of the macrophyte- to an algae-dominated state in shallow eutrophic lakes. The differentiated processes in the MDA and ADA should be given more attention during future research and management of internal P loadings in eutrophic lakes.

Dynamic Changes in Myofibroblasts Affect the Carcinogenesis and Prognosis of Bladder Cancer Associated With Tumor Microenvironment Remodeling.

Bladder cancer (BLCA) is a tumor that possesses significant heterogeneity, and the tumor microenvironment (TME) plays an important role in the development of BLCA. The TME chiefly consists of tumor cells and tumor-infiltrating immune cells admixed with stromal components. Recent studies have revealed that stromal components, especially cancer-associated fibroblasts (CAFs), affect immune cell infiltration and modulate the extracellular matrix in the TME of BLCA, ultimately impacting the prognosis and therapeutic efficacy of BLCA. Among the subgroups of CAFs, myofibroblasts (myCAFs) were the most abundant and were demonstrated to play an essential role in affecting the prognosis of various tumors, including BLCA. However, the dynamic changes in myCAFs during carcinogenesis and tumor progression have been less discussed previously. With the help of bioinformatics algorithms, we discussed the roles of myCAFs in the carcinogenesis and prognosis of BLCA in this manuscript. Our study highlighted the pathogenesis of BLCA was accompanied by a decrease in the abundance of myCAFs, revealing potential protective properties of myCAFs in the carcinogenesis of BLCA. Meanwhile, the reduced expressions of myCAFs marker genes were highly accurate in predicting tumorigenesis. In contrast, we also demonstrated that myCAFs regulated extracellular matrix remodeling, tumor metabolism, cancer stemness, and oncological mutations, ultimately impacting the treatment responsiveness and prognosis of BLCA patients. Thus, our research revealed the bimodal roles of myCAFs in the development of BLCA, which may be associated with the temporal change of the TME. The in-depth study of myofibroblasts and the TME may provide potential diagnostic biomarkers and therapeutic targets for BLCA.

Comprehensive analysis of CXCL12 expression reveals the significance of inflammatory fibroblasts in bladder cancer carcinogenesis and progression.

BACKGROUND: Bladder cancer (BLCA) is the most common genitourinary tumor but lacks specific diagnostic biomarkers. Recent years have witnessed significant advances in the use and approval of immune checkpoint blockade (ICB) therapy to manage BLCA at advanced stages when platinum-based therapy has failed. The tumor microenvironment (TME) is essential in impacting BLCA patients' prognosis and responsiveness to ICB therapy. CXCL12 is a stromal secreted factor that was essentially involved in regulating the TME among cancers. In this article, we thoroughly investigated the TME regulating roles of CXCL12 in BLCA and revealed its critical involvement in the development of BLCA, which was closely correlated with inflammatory fibroblasts (iCAFs). METHODS: We examined the gene expression profiles in the TCGA and GEO database to reveal the potential association of CXCL12 with the carcinogenesis and prognosis of BLCA. The receiver operating characteristic curve was used to explore the accuracy of CXCL12 along with multiple iCAFs-associated genes in the diagnosis of BLCA. The MCP-COUNTER, ESTIMATE, and TIDE algorithms were applied to estimate the TME components and predict immunotherapy responsiveness. An iCAFs signature was constructed using the ssGSEA algorithm. The "maftool" R package analyzed the oncogenic mutations in BLCA patients. Bioinformatics analysis results were further validated through immunohistochemistry of clinical samples. IMvigor210 cohort was used to validate bioinformatic predictions of therapeutic responsiveness to immune checkpoint inhibitors. RESULTS: This manuscript revealed a significantly reduced expression of CXCL12 in BLCA compared with normal tissue. The expressions of various marker genes for iCAFs were also reduced considerably in BLCA tissues, highlighting the reduction of iCAFs in the pathogenesis of BLCA. Further studies revealed that CXCL12 and iCAFs were associated with pathological features, TME remodeling and aging in BLCA patients. The iCAFs signature further confirmed the intricate immunomodulatory roles of iCAFs in BLCA. Gene mutation analysis revealed the essential relationship between iCAFs and the mutation frequency of oncogenic genes, including TP53 and FGFR3. Meantimes, iCAFs levels also significantly affected BLCA patients' mutations in the TP53 and RTK-RAS pathways. Finally, our results confirmed the significant exclusion of CD8 + T cells by iCAFs, which further influenced the immunotherapy responsiveness in BLCA patients. CONCLUSIONS: This article highlighted the impact of CXCL12 on the pathogenesis and progression of BLCA. The reduced expression levels of iCAFs markers, including CXCL12, were highly accurate in the diagnosis of BLCA, suggesting the reduction of iCAFs accompanied bladder carcinogenesis. However, both CXCL12 and iCAFs significantly impacted the prognosis and immunotherapy responsiveness for BLCA patients by remodeling the TME. Our results critically suggested the dual roles of iCAFs in the carcinogenesis and progression of BLCA. Further exploration of iCAFs might unravel potential diagnostic biomarkers and therapeutic targets for BLCA.

LncRNA CCAT1 promotes prostate cancer cells proliferation, migration, and invasion through regulation of miR-490-3p/FRAT1 axis.

Prostate cancer (PCa) is a prevalent cancer in males, with high incidence and mortality. Recent studies have shown the crucial role of long non-coding RNA (lncRNA) in PCa. Here, we aimed to explore the functional roles and inner mechanisms of lncRNA CCAT1 in PCa cells. qRT-PCR results showed that CCAT1 was upregulated in PCa tissues and cells. Functional assays demonstrated that CCAT1 knockdown suppressed cell proliferation, migration, invasion, yet promoted apoptosis, while CCAT1 promotion showed the opposite results. We also found that CCAT1 negatively regulated miR-490-3p expression and subsequently regulated FRAT1 expression. Inhibition of miR-490-3p or up-regulation of FRAT1 reversed the suppressive effects of CCAT1 knockdown on the PCa cells. In conclusion, CCAT1 regulated FRAT1 expression through miR-490-3p and then promote the PCa cells proliferation, migration, and invasion, which reveals the oncogenic function of CCAT1 in PCa progress.

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis.

The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients' responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine.

The cancer-associated fibroblasts related gene CALD1 is a prognostic biomarker and correlated with immune infiltration in bladder cancer.

BACKGROUND: Stromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Accumulating pieces of evidence indicate that CAFs participate in the crosstalk with tumor cells and have a complex interaction network with immune components. Further studies on the role of CAFs in the bladder cancer microenvironment and searching for possible specific markers are important for a deeper understanding of CAFs in bladder cancer progression and immunomodulation. METHODS: In the present study, we examined the abundance of CAFs in the TCGA and GEO datasets using the MCP-COUNTER algorithm. Additionally, the expression of genes related to CAFs was analyzed through the Weighted Gene Co-expression Network Analysis (WGCNA). The CIBERSORT and ESTIMATE algorithms were used to discuss the correlation of the key CAFs-related gene and the tumor microenvironment components. Immunohistochemistry analysis in clinical samples was used to validate the results of bioinformatics analysis. RESULTS: The results showed that CAFs were closely associated with the progression and prognosis of bladder cancer. WGCNA also revealed that CALD1 was a key CAFs-related gene in bladder cancer. Moreover, further in-depth analysis showed that CALD1 significantly affected the progression and prognosis of bladder cancer. The CIBERSORT and ESTIMATE algorithms demonstrated significant correlations between CALD1 and the tumor microenvironment components, including CAFs, macrophages, T cells, and multiple immune checkpoint related genes. Finally, immunohistochemistry results validated the strong association of CALD1 with CAFs and macrophages. CONCLUSIONS: In the present study, we confirmed the cancer-promoting roles of CAFs in bladder cancer. Being a key gene associated with CAFs, CALD1 may promote bladder cancer progression by remodeling the tumor microenvironment. The bioinformatics methods, including the CIBERSORT, MCP-COUNTER and ESTIMATE algorithms, may provide important value for studying the tumor microenvironment.

Identification and Validation of a Stromal EMT Related LncRNA Signature as a Potential Marker to Predict Bladder Cancer Outcome.

Bladder cancer (BLCA) has become one of the most common malignant tumors in the genitourinary system. BLCA is one of the tumors considered suitable for immunotherapy because of the large proportion of immune cells in TME. Epithelial to mesenchymal transition (EMT) is closely related to tumor immunity through its crosstalk with immune cells. A recent study validated that EMT-related genes were mainly expressed by stromal cells and could influence immunotherapy responsiveness. Stromal EMT-related gene signature was also demonstrated to affect the prognosis of multiple tumors, including BLCA. To further explore the prognostic roles of stromal components, we performed a comprehensive analysis of LncRNAs closely associated with stromal EMT-related genes in the TCGA BLCA cohort. We identified a signature including five stromal EMT gene-related LncRNAs that showed significant prognostic value for BLCA patients. By the CIBERSORT and MCP-COUNTER algorithm, we found the signature was markedly correlated with infiltrated immune cells and stromal components of the tumor microenvironment, which may further influence patient's responsiveness to immune checkpoint blockade therapy. Through immunohistochemical analysis, we confirmed the correlation of the signature with macrophages M2 and CAFs. Meanwhile, key genes related to these LncRNAs, including VIM, MMP2, were also differentially expressed in the stromal components concerning the signature. Our research confirmed the prognostic and immune-associated role of stromal EMT-related LncRNAs. Meantime, we further confirmed that EMT-related genes were mainly expressed in stromal components. Targeting these LncRNAs as well as their related stromal EMT genes may provide potential therapeutic targets for BLCA immunotherapy and precision medicine.

[Effects of Xiao-Cheng-Qi decoction on brain edema and inflammatory factors in rats with severe traumatic brain injury].

OBJECTIVE: To observe the effects of the Chinese medicine prescription Xiao-Cheng-Qi decoction (XCQD) on acute brain edema and inflammatory factors in rats with severe traumatic brain injury (sTBI). METHODS: A total of 108 male Sprague-Dawley (SD) rats were divided into control group, sham operation group, sTBI model group, and XCQD low, medium, high dose groups by random number table method, with 18 rats in each group. sTBI rat model was prepared according to the modified Freeney method. At 6 hours after injury, the XCQD low, medium, and high dose groups were given XCQD 1.80, 2.78, and 4.59 g/kg by gavage, respectively, and the other three groups were given the same amount of normal saline, once a day for 3 days. After 3 days of injury, rats in each group were sacrificed after the modified neurologic severity score (mNSS) assessed. Pathological changes of brain tissue were observed under light microscope after hematoxylin eosin (HE) staining, water content of brain tissue was measured by dry-wet specific gravity method, and the expressions of aquaporin 4 (AQP4), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in brain tissue were detected by Western blotting. Serum TNF-α and IL-1ß levels were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the normal group, the mNSS score of rats increased significantly, the structure of brain tissue was disordered, and pathological changes appeared such as inflammation, edema, pyknosis of nerve nuclei, water content, the protein expressions of AQP4, TNF-α and IL-1ß in brain tissue, and the contents of TNF-α, IL-1ß in serum were significantly increased. After XCQD intervention, the above indexes were significantly improved. Compared with sTBI model group, the mNSS score of XCQD medium and high dose groups significantly decreased (6.94±1.16, 6.88±1.02 vs. 8.61±1.09, both P < 0.05), and the pathological changes such as brain edema and inflammation were alleviated. Brain tissue water content, AQP4 protein expression and contents of serum TNF-α, IL-1ß in XCQD low, medium, and high dose groups significantly decreased compared with sTBI model group [brain tissue water content: (78.25±0.71)%, (77.62±0.44)%, (76.70±0.74)% vs. (80.08±0.66)%; the expression of brain AQP4 protein (AQP4/ß-actin): 0.86±0.13, 0.84±0.22, 0.65±0.13 vs. 1.08±0.14; serum TNF-α (ng/L): 106.34±15.07, 95.75±17.26, 89.00±17.36 vs. 141.96±29.47; serum IL-1ß (ng/L): 90.41±12.88, 72.82±13.51, 71.32±16.79 vs. 128.57±22.56, respectively, all P < 0.05]. The protein expressions of TNF-α,IL-1ß in brain tissue of XCQD medium and high dose groups also significantly decreased compared with sTBI model group [TNF-α (TNF-α/ß-actin): 0.90±0.24, 0.79±0.35 vs. 1.17±0.15; IL-1ß (IL-1ß/ß-actin): 0.91±0.21, 0.68±0.28 vs. 1.23±0.08, respectively, all P < 0.05]. Brain tissue water content, the expression of brain AQP4 protein, the levels of brain tissue and serum IL-1ß in XCQD high dose group improved more significant than those of XCQD low dose group. CONCLUSIONS: XCQD can alleviate the acute brain edema in sTBI rats, and it is dose-dependent. The mechanism may be relevant to reduce the secondary inflammatory response of sTBI by inhibiting the expression of inflammatory factors TNF-α and IL-1ß.

Contrasting exchanges of nitrogen and phosphorus across the sediment-water interface during the drying and re-inundation of littoral eutrophic sediment.

High water level fluctuations (WLFs) lead to periodic drying and re-inundation of sediments in the littoral area of eutrophic lakes. In this study, a series of littoral sediment cores were dried for different periods (5-30 d) and rewetted for 48 h. The sediment cores that dried for 30 d were then re-inundated for 90 d. The exchanges of nitrogen (N) and phosphorus (P) across the sediment-water interface (SWI) and the mechanisms were studied. The results showed that ammonium nitrogen (NH4+-N) fluxes increased after 5-25 d of drying, which was followed by an obvious decrease after 30 d of drying. The decreased NH4+-N fluxes remained at low levels during the 90 d re-inundation period. The soluble reactive P (SRP) fluxes decreased significantly after 15 d of drying. However, further re-inundation increased the SRP fluxes to their initial levels. The decreased water content and porosity, the oxidation of the sediment during drying, and the associated transformations of the N and P fractions in the sediment from drying to re-inundation influenced the exchanges of NH4+-N and SRP across the SWI. The decrease of labile NH4+-N in the sediment during drying was non-reversible, while the transformations between redox sensitive P (Fe-P) and aluminum-bound P were more likely to be reversible from drying to re-inundation. The increase of Fe-P during drying and dissolution of Fe-P during the re-inundation were responsible for the development of SRP fluxes from drying to re-inundation. Therefore, the periodic drying and re-inundation of the littoral eutrophic sediments reduced the release of NH4+-N but accelerated the release of SRP from the sediment. This should be given more consideration for the remediation and management of eutrophication in the lake and other similar lakes with high WLFs.

Full-Differential Folded-Cascode Front-End Receiver Amplifier Integrated Circuit for Capacitive Micromachined Ultrasonic Transducers.

This paper describes the design of a front-end receiver amplifier for capacitive micromachined ultrasonic transducer (CMUT). The proposed operational amplifier (op amp) consists of a full differential folded-cascode amplifier stage followed by a class AB output stage. A feedback resistor is applied between the input and the output of the op amp to make a transimpedance amplifier. We analyzed the equivalent circuit model of the CMUT element operating in the receiving mode and obtained the static output impedance and center frequency characteristics of the CMUT. The op amp gain, bandwidth, noise, and power consumption trade-offs are discussed in detail. The amplifier was fabricated using GlobalFoundries 0.18-µm complementary metal-oxide-semiconductor (CMOS) technology. The open loop gain of the amplifier is approximately 65 dB, and its gain bandwidth product is approximately 29.5 MHz. The measured input reference noise current was 56 nA/√Hz@3 MHz. The amplifier chip area is 325 µm × 150 µm and the op amp is powered by 3.3 V, the static power consumption is 11 mW. We verified the correct operation of our amplifier with CMUT and echo-pulse shown that the CMUT center frequency is 3 MHz with 92% fractional bandwidth.