Single-cell sequencing reveals the heterogeneity of B cells and tertiary lymphoid structures in muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. B cells are crucial factors in tumor suppression, and tertiary lymphoid structures (TLSs) facilitate immune cell recruitment to the tumor microenvironment (TME). However, the function and mechanisms of tumor-infiltrating B cells and TLSs in MIBC need to be explored further. METHODS: We performed single-cell RNA sequencing analysis of 11,612 B cells and 55,392 T cells from 12 bladder cancer patients and found naïve B cells, proliferating B cells, plasma cells, interferon-stimulated B cells and germinal center-associated B cells, and described the phenotype, gene enrichment, cell-cell communication, biological processes. We utilized immunohistochemistry (IHC) and immunofluorescence (IF) to describe TLSs morphology in MIBC. RESULTS: The interferon-stimulated B-cell subtype (B-ISG15) and germinal center-associated B-cell subtypes (B-LMO2, B-STMN1) were significantly enriched in MIBC. TLSs in MIBC exhibited a distinct follicular structure characterized by a central region of B cells resembling a germinal center surrounded by T cells. CellChat analysis showed that CXCL13 + T cells play a pivotal role in recruiting CXCR5 + B cells. Cell migration experiments demonstrated the chemoattraction of CXCL13 toward CXCR5 + B cells. Importantly, the infiltration of the interferon-stimulated B-cell subtype and the presence of TLSs correlated with a more favorable prognosis in MIBC. CONCLUSIONS: The study revealed the heterogeneity of B-cell subtypes in MIBC and suggests a pivotal role of TLSs in MIBC outcomes. Our study provides novel insights that contribute to the precision treatment of MIBC.

Proteomic profiling of prostate cancer reveals molecular signatures under antiandrogen treatment.

BACKGROUND: Tumorigenesis and progression of prostate cancer (PCa) are indispensably dependent on androgen receptor (AR). Antiandrogen treatment is the principal preference for patients with advanced PCa. However, the molecular characteristics of PCa with antiandrogen intervention have not yet been fully uncovered. METHODS: We first performed proteome analysis with 32 PCa tumor samples and 10 adjacent tissues using data-independent acquisition (DIA)- parallel accumulation serial fragmentation (PASEF) proteomics. Then label-free quantification (LFQ) mass spectrometry was employed to analyze protein profiles in LNCaP and PC3 cells. RESULTS: M-type creatine kinase CKM and cartilage oligomeric matrix protein COMP were demonstrated to have the potential to be diagnostic biomarkers for PCa at both mRNA and protein levels. Several E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) were significantly altered in PCa and PCa cells under enzalutamide treatment, and these proteins might reprogram proteostasis at protein levels in PCa. Finally, we discovered 127 significantly varied proteins in PCa samples with antiandrogen therapy and further uncovered 4 proteins in LNCaP cells upon enzalutamide treatment. CONCLUSIONS: Our research reveals new potential diagnostic biomarkers for prostate cancer and might help resensitize resistance to antiandrogen therapy.

Population-based BRCA germline mutation screening in the Han Chinese identifies individuals at risk of BRCA mutation-related cancer: experience from a clinical diagnostic center from greater Shanghai area.

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers. RESULTS: Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months). CONCLUSION: The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.

Birnessite-Type MnO2 Modified Sustainable Biomass Fiber toward Adsorption Removal Heavy Metal Ion from Actual River Aquatic Environment.

In this work, a novel birnessite-type MnO2 modified corn husk sustainable biomass fiber (MnO2@CHF) adsorbent was fabricated for efficient cadmium (Cd) removal from aquatic environments. MnO2@CHF was designed from KMnO4 hydrothermally treated with corn husk fibers. Various characterization revealed that MnO2@CHF possessed the hierarchical structure nanosheets, large specific surface area, and multiple oxygen-containing functional groups. Batch adsorption experimental results indicated that the highest Cd (II) removal rate could be obtained at the optimal conditions of adsorbent amount of 0.200 g/L, adsorption time of 600 min, pH 6.00, and temperature of 40.0 °C. Adsorption isotherm and kinetics results showed that Cd (II) adsorption behavior on MnO2@CHF was a monolayer adsorption process and dominated by chemisorption and intraparticle diffusion. The optimum adsorption capacity (Langmuir model) of Cd (II) on MnO2@CHF was 23.0 mg/g, which was higher than those of other reported common biomass adsorbent materials. Further investigation indicated that the adsorption of Cd (II) on MnO2@CHF involved mainly ion exchange, surface complexation, redox reaction, and electrostatic attraction. Moreover, the maximum Cd (II) removal rate on MnO2@CHF from natural river samples (Xicheng Canal) could reach 59.2% during the first cycle test. This study showed that MnO2@CHF was an ideal candidate in Cd (II) practical application treatment, providing references for resource utilization of agricultural wastes for heavy metal removal.

Contributions of selenium-oxidizing bacteria to selenium biofortification and cadmium bioremediation in a native seleniferous Cd-polluted sandy loam soil.

Selenium (Se) is a trace element that is essential for human health. Daily dietary Se intake is governed by the food chain through soil-plant systems. However, the cadmium (Cd) content tends to be excessive in seleniferous soil, in which Se and Cd have complex interactions. Therefore, it is a great challenge to grow crops containing appreciable amounts of Se but low amounts of Cd. We compared the effects of five Se-transforming bacteria on Se and Cd uptake by Brassica rapa L. in a native seleniferous Cd-polluted soil. The results showed that three Se-oxidizing bacteria (LX-1, LX-100, and T3F4) increased the Se content of the aboveground part of the plant by 330.8%, 309.5%, and 724.3%, respectively, compared to the control (p < 0.05). The three bacteria also reduced the aboveground Cd content by 15.1%, 40.4%, and 16.4%, respectively (p < 0.05). In contrast, the Se(IV)-reducing bacterium ES2-45 and weakly Se-transforming bacterium LX-4 had no effect on plant Se uptake, although they did decrease the aboveground Cd content. In addition, the three Se-oxidizing bacteria increased the Se available in the soil by 38.4%, 20.4%, and 24.0%, respectively, compared to the control (p < 0.05). The study results confirm the feasibility of using Se-oxidizing bacteria to simultaneously enhance plant Se content and reduce plant Cd content in seleniferous Cd-polluted soil.

SIRT2 promotes cell proliferation and migration through mediating ERK1/2 activation and lactosylceramide accumulation in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is an age-related malignancy with a high incidence and mortality rate due to lack of efficacy drugs for its therapy in late castration-resistant stage. Sirtuin 2 (SIRT2), a NAD+ -dependent protein deacetylase, is associated with age-related diseases. However, SIRT2 roles in PCa are unclear yet. METHODS: Data of SIRT2 expression were extracted from TCGA cohort and GSE54460 cohort. Realtime quantitative PCR and immunohistochemistry were employed to analyze the expression of SIRT2 in PCa tissues. Cell counting Kit-8 assay, lentiviral transduction, flow cytometry, transwell experiments, western blot and metabolomic analysis were performed to explore the functions of SIRT2. RESULTS: SIRT2 exhibited increased expression in castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Overexpression of SIRT2 promoted cell proliferation, the proportion of S phase, migration and invasion, and reduced apoptosis rate. The increased phosphorylated ERK1/2 indicated the regulation of SIRT2 to cell proliferation, migration and invasion through activation of ERK1/2 pathway. Furthermore, SIRT2 affected cell metabolic profile and induces lactosylceramide production through upregulation of B4GALT5, which further contributes cell migration and invasion. CONCLUSIONS: Our data suggested that SIRT2 is overexpressed in CRPC and NEPC and could promote cell growth and migration through activating ERK1/2 pathway and inducing lactosylceramide production, indicating that SIRT2 has the potential to be a new target for the treatment of PCa.

Direct Separation of UO2 2+ by Coordination Sieve Effect via Spherical Coordination Traps.

Molecule sieve effect (MSE) can enable direct separation of target, thus overcoming two major scientific and industrial separation problems in traditional separation, coadsorption, and desorption. Inspired by this, herein, the concept of coordination sieve effect (CSE) for direct separation of UO2 2+ , different from the previously established two-step separation method, adsorption plus desorption is reported. The used adsorbent, polyhedron-based hydrogen-bond framework (P-HOF-1), made from a metal-organic framework (MOF) precursor through a two-step postmodification approach, afforded high uptake capacity (close to theoretical value) towards monovalent Cs+ , divalent Sr2+ , trivalent Eu3+ , and tetravalent Th4+ ions, but completely excluded UO2 2+ ion, suggesting excellent CSE. Direct separation of UO2 2+ can be achieved from a mixed solution containing Cs+ , Sr2+ , Eu3+ , Th4+ , and UO2 2+ ions, giving >99.9% removal efficiency for Cs+ , Sr2+ , Eu3+ , and Th4+ ions, but <1.2% removal efficiency for UO2 2+ , affording benchmark reverse selectivity (SM/U ) of >83 and direct generation of high purity UO2 2+ (>99.9%). The mechanism for such direct separation via CSE, as unveiled by both single crystal X-ray diffraction and density-functional theory (DFT) calculation, is due to the spherical coordination trap in P-HOF-1 that can exactly accommodate the spherical coordination ions of Cs+ , Sr2+ , Eu3+ , and Th4+ , but excludes the planar coordination UO2 2+ ion.

The optimal intravesical maintenance chemotherapy scheme for the intermediate-risk group non-muscle-invasive bladder cancer.

OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.

Robust Six-Connected Self-Penetrating Net with Two-Fold Interpenetration for Trace SO2 Removal and UO22+ Detection.

We reported in this work a new metal-organic framework, ECUT-177, showing a highly rare six-connected net with both self-penetrating and interpenetrating features. More interestingly, ECUT-177 also enables promising applications in both trace SO2 capture and luminescence sensing of uranyl.

Effect of Enhanced Hydrolytic Acidification Process on the Treatment of Azo Dye Wastewater.

The hydrolysis acidification process is an economical and effective method, but its efficiency is still low in treating azo dye wastewater. It is therefore crucial to find more suitable and efficient means or techniques to further strengthen the process of treating azo dye wastewater by a hydrolytic acidification process. In this study, a hydrolytic acidification aerobic reactor was used to simulate the azo dye wastewater process. The change of wastewater quality during the reaction process was monitored, and the deep enhancement effect of single or composite biological intensification technology on the treatment of azo dye wastewater by the hydrolytic acidification process was also explored. Co-substrate strengthening and the addition of fructose co-substrate can significantly improve the efficiency of hydrolytic acidification. Compared with the experimental group without the addition of fructose, the decolorization ratio of wastewater was higher (93%) after adding fructose co-substrate. The immobilization technology was strengthened, and the immobilized functional bacteria DDMZ1 pellet was used to treat the simulated azo dye wastewater. The results showed that the composite technology experimental group with the additional fructose co-matrix had a better decolorization efficiency than the single immobilized bio-enhancement technology, with the highest decolorization ratio of 97%. As a composite biological intensification method, the fructose co-matrix composite with immobilized functional bacteria DDMZ1 technology can be applied to the treatment of azo dye wastewater.

LncRNA00492 is required for marginal zone B-cell development.

B-cell development undergoes a series of steps from the bone marrow to the secondary lymphoid organs. A defect in B-cell development can lead to immunodeficiency or malignant disorders, such as leukaemia or lymphoma. Long non-coding RNAs have been reported to act as important regulators of many pathological processes. However, very little is known regarding the role of lncRNAs during B-cell development and the regulation of their expression. In this study, we explored the expression and role of lncRNA Gme00492 in B-cell development. We observed that lnc00492 was highly expressed in B-cell development and primarily expressed in the nucleus. Lnc00492-deficient mice had fewer marginal zone B cells in the spleen, likely due to a developmental block. Importantly, lnc00492 interacts with CTBP1 and targets it for ubiquitination and degradation during B-cell development, whereas the transcriptional corepressor factor CTBP1 plays a critical role in Notch2 signalling. Thus, we identified a novel regulatory axis between lnc00492 and CTBP1 in B cells, suggesting that lnc00492 is essential for marginal zone B-cell development.

Correlation between Body Mass Index and Cognitive Function in Patients with Atrial Fibrillation.

Background: Evidence regarding the relationship between body mass index (BMI) and cognitive function was limited. Therefore, the objective of this research is to investigate whether BMI is independently related to cognitive function in Chinese patients with atrial fibrillation after adjusting for other covariates. Methods: The present study is a cross-sectional study. A total of 281 patients with atrial fibrillation who were hospitalized at the Affiliated Hospital of Jining Medical University in Shandong Province from January 2021 to November 2021 were included in the study. The target independent variable and the dependent variable were BMI and cognitive function in patients with atrial fibrillation, respectively. The patients' general information, BMI, past history, medication history, and other disease-related data were collected. The Montreal cognitive assessment scale (MoCA) was used to evaluate cognitive function. Results: A total of 244 patients with atrial fibrillation were collected in this study, with an average age of (67.28 ± 10.33) years, of whom 55.3% were male. The average BMI was (25.33 ± 4.27) kg/m2, and the average cognitive function score was (19.25 ± 6.88) points. The results of the smooth curve fitting and threshold effect tests showed that there was a curve correlation between BMI and cognitive function score, and its inflection point was 24.56 kg/m2. To the left of the inflection point, the relationship was significant; the effect size and the confidence interval were 0.43 and 0.01-0.85, respectively. To the right of the inflection point, there was no significant correlation between BMI and cognitive function (P=0.152). Conclusion: When BMI is lower than 24.56 kg/m2, the cognitive function score increases by 0.43 points for each unit increase in BMI in patients with atrial fibrillation. An increase in BMI at this time is a protective factor for cognitive function. Within the normal range of BMI, the higher the BMI in atrial fibrillation patients, the higher the cognitive function score. We encourage atrial fibrillation patients with normal BMI to maintain their current weight.

Effect of rock salt aerosol therapy on quality of life of patients with pneumoconiosis: A multicenter, randomized, double-blind clinical trial.

This study aimed to explore the impact of rock salt aerosol therapy on the quality of life in pneumoconiosis patients. It may provide new treatment method for the comprehensive control of pneumoconiosis. A total of 452 subjects from 6 hospitals were divided based on the multi-level hierarchical random design. The patients in the treatment group received conventional comprehensive treatment + rock salt aerosol therapy. The baseline data were collected, including gender, age, age of dust exposure, stage and COPD combination. Cough, expectoration and dyspnea levels were valuated. Both of the two methods exhibited good curative effect following time extension. Rock salt aerosol therapy showed more significant effect compared with routine method. The clinical symptom tends to be stable after two weeks treatment of rock salt aerosol therapy. The curative effect increases with the extension of treatment time. 2-4 weeks for one course of treatment can improve the curative effect. Rock salt aerosol therapy can effectively improve the quality of life of pneumoconiosis patients. It is a good treatment and rehabilitation method for the prevention and treatment of pneumoconiosis, thus is worthy of clinical application.

Granulocyte colony-stimulating factor directly acts on mouse lymphoid-biased but not myeloid-biased hematopoietic stem cells.

Granulocyte colony-stimulating factor (G-CSF) is widely used in clinical settings to mobilize hematopoietic stem cells (HSCs) into the circulation for HSC harvesting and transplantation. However, whether G-CSF directly stimulates HSCs to change their cell cycle state and fate is controversial. HSCs are a heterogeneous population consisting of different types of HSCs, such as myeloid-biased HSCs and lymphoid-biased HSCs. We hypothesized that G-CSF has different effects on different types of HSCs. To verify this, we performed serum-free single-cell culture and competitive repopulation with cultured cells. Single highly purified HSCs and hematopoietic progenitor cells (HPCs) were cultured with stem cell factor (SCF), SCF + G-CSF, SCF + granulocyte/macrophage (GM)-CSF, or SCF + thrombopoietin (TPO) for 7 days. Compared with SCF alone, SCF + G-CSF increased the number of divisions of cells from the lymphoid-biased HSC-enriched population but not that of cells from the My-bi HSC-enriched population. SCF + G-CSF enhanced the level of reconstitution of lymphoid-biased HSCs but not that of myeloid-biased HSCs. Clonal transplantation assay also showed that SCF + G-CSF did not increase the frequency of myeloid-biased HSCs. These data showed that G-CSF directly acted on lymphoid-biased HSCs but not myeloid-biased HSCs. Our study also revised the cytokine network at early stages of hematopoiesis: SCF directly acted on myeloid-biased HSCs; TPO directly acted on myeloid-biased HSCs and lymphoid-biased HSCs; and GM-CSF acted only on HPCs. Early hematopoiesis is controlled differentially and sequentially by a number of cytokines.

The Treatment Strategy for Skull Base Reconstruction for Anterior Cranial Fossa Intra- and Extracranial Tumors.

ABSTRACT: Anterior cranial fossa intra- and extracranial tumors arise from the anterior cranial fossa and invade the orbit and nose. Anterior cranial fossa tumor resection and skull base reconstruction are challenging for neurosurgeons due to the complex anatomy, leakage of cerebrospinal fluid, and critical neurovasculature involvement. The authors report a case series of cranio-orbital communicating tumors and cranionasal-orbital communicating tumors. All patients underwent a modified Derome approach or transfrontal basal approach, and all tumor resections were satisfactory. Skull base reconstruction for small defects (<1.5 cm) can be performed with autogenous fascia, muscle, and fat. Large defects (≥1.5 cm) require autogenous fascia, muscle, and fat combined with osseous reconstruction (autogenous bone, titanium mesh, and polyetheretherketone). The techniques and treatments were successful, and only 1 patient experienced mild cerebrospinal fluid leak but no intracranial infection, pneumocrania or intracranial hemorrhage. Additionally, long-term follow-up demonstrated that the outcomes remain favorable. According to a literature review, this technique might be an alternative strategy for treating anterior cranial fossa intra- and extracranial tumors, and better skull base reconstruction can prevent many postoperative complications.

Bionic Integrated Positioning Mechanism Based on Bioinspired Polarization Compass and Inertial Navigation System.

In this paper, to address the problem of positioning accumulative errors of the inertial navigation system (INS), a bionic autonomous positioning mechanism integrating INS with a bioinspired polarization compass is proposed. In addition, the bioinspired positioning system hardware and the integration model are also presented. Concerned with the technical issue of the accuracy and environmental adaptability of the integrated positioning system, the sun elevation calculating method based on the degree of polarization (DoP) and direction of polarization (E-vector) is presented. Moreover, to compensate for the latitude and longitude errors of INS, the bioinspired positioning system model combining the polarization compass and INS is established. Finally, the positioning performance of the proposed bioinspired positioning system model was validated via outdoor experiments. The results indicate that the proposed system can compensate for the position errors of INS with satisfactory performance.

Variation and comparison of biotoxicity during typical biological treatment of dyeing wastewater.

In present study, dyeing wastewater samples were collected from three typical dyeing wastewater treatment plants in Wujiang, Shengze and Shanghai, China. Physicochemical properties and biotoxicity indicators (luminescent bacteria acute toxicity and umu genotoxicity) were tested and the relationships among them were analyzed. The results revealed that two biotoxicity indicators varied significantly among different treatment units of three plants. After treatment by plant A, luminescent bacteria acute toxicity of dyeing wastewater reduced effectively, while umu genotoxicity increased significantly. Two biotoxicity indicators exhibited decrease and increase trends during the treatment processes of plant B and plant C, respectively. Correlation analysis indicated that there was little correlation among biotoxicity indicators and physicochemical properties, meanwhile two kinds of biotoxicity indicators were relatively independent. Therefore, it was recommended that comprehensive evaluation of dyeing wastewater toxicity needs the combination of various biotoxicity indicators, and the relationship among biotoxicity indicators and physicochemical properties of dyeing wastewater should be established individually. The results of this study would offer a general understanding and evaluation of biotoxicity during actual dyeing wastewater treatment processes and provide database for toxicity reduction and management of dyeing wastewater.

Psychological impact of 2019 novel coronavirus (2019-nCoV) outbreak in health workers in China.

The first case of 2019-nCoV pneumonia infection occurred in Wuhan, Hubei Province, South China Seafood Market in December 2019. As a group with a high probability of infection, health workers are faced with a certain degree of psychological challenges in the process of facing the epidemic. This study attempts to evaluate the impact of 2019-nCoV outbreak on the psychological state of Chinese health workers and to explore the influencing factors. During the period from 31 January 2020 to 4 February 2020, the 'Questionnaire Star' electronic questionnaire system was used to collect data. The 2019-nCoV impact questionnaire and The Impact of Event Scale (IES) were used to check the psychological status of health workers in China. A total of 442 valid data were collected in this study. Seventy-four (16.7%) male and 368 (83.3%) female individuals participated in this study. The average score of high arousal dimension was 5.15 (s.d. = 4.71), and the median score was 4.0 (IQR 2.0, 7.0). The average score of IES was 15.26 (s.d. = 11.23), and the median score was 13.5 (IQR 7.0, 21.0). Multiple regression analysis showed that there were critical statistical differences in high arousal scores among different gender groups (male 3.0 vs. female 5.0, P = 0.075). Whether being quarantined had significant statistical differences of IES scores (being quarantined 16.0 vs. not being quarantined 13.0, P = 0.021). The overall impact of the 2019-nCoV outbreak on health workers is at a mild level. Chinese health workers have good psychological coping ability in the face of public health emergencies.

Single-Cell Transcriptomic Map of the Human and Mouse Bladders.

BACKGROUND: Having a comprehensive map of the cellular anatomy of the normal human bladder is vital to understanding the cellular origins of benign bladder disease and bladder cancer. METHODS: We used single-cell RNA sequencing (scRNA-seq) of 12,423 cells from healthy human bladder tissue samples taken from patients with bladder cancer and 12,884 cells from mouse bladders to classify bladder cell types and their underlying functions. RESULTS: We created a single-cell transcriptomic map of human and mouse bladders, including 16 clusters of human bladder cells and 15 clusters of mouse bladder cells. The homology and heterogeneity of human and mouse bladder cell types were compared and both conservative and heterogeneous aspects of human and mouse bladder evolution were identified. We also discovered two novel types of human bladder cells. One type is ADRA2A+ and HRH2+ interstitial cells which may be associated with nerve conduction and allergic reactions. The other type is TNNT1+ epithelial cells that may be involved with bladder emptying. We verify these TNNT1+ epithelial cells also occur in rat and mouse bladders. CONCLUSIONS: This transcriptomic map provides a resource for studying bladder cell types, specific cell markers, signaling receptors, and genes that will help us to learn more about the relationship between bladder cell types and diseases.

MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta in breast cancer.

Lysosomal-associated protein transmembrane 4 beta (LAPTM4B), a proto-oncogene, has been shown to be a positive modulator in cancer progression. However, the mechanism of LAPTM4B regulation is not fully elucidated. Aberrant microRNAs (miRNAs) can regulate gene expression by interfering with target transcripts and/or translation to exert tumor-suppressive or oncogenic effects in breast cancer. In the present study, miR-132-3p, which was predicted by relevant software, was confirmed to directly bind to the 3' untranslated region (3'UTR) of LAPTM4B and negatively regulate its expression in luciferase reporter and western blot assays. Subsequently, we validated that miR-132-3p was downregulated in breast cancer tissues. Receiver-operating characteristic curve analysis indicated that miR-132-3p had accurate diagnostic value, and a Kaplan-Meier and Cox regression model showed that miR-132-3p was a potential prognostic marker for recurrence, showing low levels in breast cancer patients. In addition, we showed that miR-132-3p was inversely correlated with LAPTM4B expression in the above samples. Functionally, miR-132-3p suppressed the migration and invasion of breast carcinoma cells through LAPTM4B by mediating epithelial-mesenchymal transition signals, and partially reversed the carcinogenic effects of LAPTM4B by inhibiting the PI3K-AKT-mTOR signaling pathway. Taken together, these findings provide the first comprehensive analysis of miR-132-3p as a direct LAPTM4B-targeted miRNA, and shed light on miR-132-3p/LAPTM4B as a significant functional axis involved in the oncogenesis and metastasis of breast cancer.