Electrically empowered microcomb laser.

Optical microcomb underpins a wide range of applications from communication, metrology, to sensing. Although extensively explored in recent years, challenges remain in key aspects of microcomb such as complex soliton initialization, low power efficiency, and limited comb reconfigurability. Here we present an on-chip microcomb laser to address these key challenges. Realized with integration between III and V gain chip and a thin-film lithium niobate (TFLN) photonic integrated circuit (PIC), the laser directly emits mode-locked microcomb on demand with robust turnkey operation inherently built in, with individual comb linewidth down to 600 Hz, whole-comb frequency tuning rate exceeding 2.4 × 1017 Hz/s, and 100% utilization of optical power fully contributing to comb generation. The demonstrated approach unifies architecture and operation simplicity, electro-optic reconfigurability, high-speed tunability, and multifunctional capability enabled by TFLN PIC, opening up a great avenue towards on-demand generation of mode-locked microcomb that is of great potential for broad applications.

Nociceptor Neurons are Involved in the Host Response to Escherichia coli Urinary Tract Infections.

Purpose: Urinary tract infections (UTIs) can evoke a rapid host immune response leading to bladder inflammation and epithelial damage. Neuroimmune interactions are critical for regulating immune function in mucosal tissues. Yet the role of nociceptor neurons in bladder host defense has not been well defined. This study aimed to explore the interaction between nociceptor neurons and bladder immune system during UTIs. Methods: In this study, whether uropathogenic Escherichia coli (UPEC) and lipopolysaccharide (LPS) can directly stimulate nociceptor neurons was detected. Female C57BL/6J mice were treated with high dose of capsaicin, a high-affinity TRPV1 agonist, to ablate nociceptor neurons. Bladder inflammation, barrier epithelial function and bladder immune cell infiltration were assessed after UPEC infection. The level of neuropeptide calcitonin gene-related peptide (CGRP) in infected bladder was detected. Furthermore, the effects of CGRP on neutrophils and macrophages were evaluated both in vitro and in vivo. Results: We found that UPEC and its pathogenic factor LPS could directly excite nociceptor neurons, releasing CGRP into infected bladder, which suppressed the recruitment of neutrophils, the polarization of macrophages and the killing function of UPEC. Both Botulinum neurotoxin A (BoNT/A) and BIBN4096 (CGRP antagonism) blocked neuronal inhibition and prevented against UPEC infection. Conclusion: The present study showed a novel mechanism by which UPEC stimulated the secretion of CGRP from nociceptor neurons to suppress innate immunity.

Prognostic Role of the Ubiquitin Proteasome System in Clear Cell Renal Cell Carcinoma: A Bioinformatic Perspective.

Background: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system. The ubiquitin proteasome system (UPS) plays an important role in the generation, metabolism and survival of tumor. We are aimed to make a comprehensive exploration of the UPS's role in ccRCC with bioinformatic tools, which may contribute to the understanding of UPS in ccRCC, and give insight for further research. Methods: The UPS-related genes (UPSs) were collected by an integrative approach. The expression and clinical data were downloaded from TCGA database. R soft was used to perform the differentially expressed UPSs analysis, functional enrichment analysis. We also estimated prognostic value of each UPS with the help of GEPIA database. Two predicting models were constructed with the differentially expressed UPSs and prognosis-related genes, respectively. The correlations of risk score with clinical characteristics were also evaluated. Data of GSE29609 cohort were obtained from GEO database to validate the prognostic models. Results: We finally identified 91 differentially expressed UPSs, 48 prognosis related genes among them, and constructed a prognostic model with 18 UPSs successfully, the AUC was 0.760. With the help of GEPIA, we found 391 prognosis-related UPSs, accounting for 57.84% of all UPSs. Another prognostic model was constructed with 28 prognosis-related genes of them, and with a better AUC of 0.825. Additionally, our models can also stratify patients into high and low risk groups accurately in GSE29609 cohort. Similar prognostic values of our models were observed in the validated GSE29609 cohort. Conclusions: UPS is dysregulated in ccRCC. UPS related genes have significant prognostic value in ccRCC. Models constructed with UPSs are effective and applicable. An abnormal ubiquitin proteasome system should play an important role in ccRCC and be worthy of further study.

Metformin ameliorates bladder dysfunction in a rat model of partial bladder outlet obstruction.

Alteration of bladder morphology and function was the most important consequence of bladder outlet obstruction (BOO). Using a rat model of partial BOO (pBOO), we found that rats treated with metformin showed lower baseline pressures with a reduced inflammatory reaction in the early phase (2 wk) after pBOO. The NLR family pyrin domain containing 3 inflammasome pathway was inhibited in pBOO rat bladders with treatment of metformin in the early phase. Metformin reduced the activity of NLR family pyrin domain containing 3 in primary urothelial cells. In the chronic phase (9 wk after pBOO), metformin treatment ameliorated bladder fibrosis and improved the reduced compliance. Treatment with metformin suppressed the activation of Smad3 and compensated the diminished autophagy in 9-wk pBOO rat bladders. Autophagy was inhibited with upregulation of profibrotic proteins in primary fibroblasts from chronic pBOO bladders, which could be restored by administration of metformin. The antifibrotic effects of metformin on fibroblasts were diminished after silencing of AMP-activated protein kinase or light chain 3B. In summary, this study elucidates that oral administration of metformin relieves inflammation in the bladder during the early phase of pBOO. Long-term oral administration of metformin can prevent functional and histological changes in the pBOO rat bladder. The current study suggests that metformin might be used to prevent the development of bladder dysfunction secondary to BOO.NEW & NOTEWORTHY The present study in a rat model showed that oral administration of metformin alleviated inflammation following partial bladder outlet obstruction in the early phase and ameliorated bladder fibrosis as well as bladder dysfunction by long-term treatment. Our study indicated that metformin is a potential drug to inhibit bladder remodeling and alleviate bladder dysfunction. Clinical trials are needed to validate the effect of metformin on the bladder dysfunction and bladder fibrosis in the future.

Single-cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics.

OBJECTIVES: Much of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number of marker genes. To have a comprehensive map of the cellular anatomy of bladder urothelial cells, we performed single-cell RNA sequencing to thoroughly characterize mouse bladder urothelium. MATERIALS AND METHODS: A total of 18,917 single cells from mouse bladder urothelium were analysed by unbiased single-cell RNA sequencing. The expression of the novel cell marker was confirmed by immunofluorescence using urinary tract infection models. RESULTS: Unsupervised clustering analysis identified 8 transcriptionally distinct cell subpopulations from mouse bladder urothelial cells. We discovered a novel type of bladder urothelial cells marked by Plxna4 that may be involved with host response and wound healing. We also found a group of basal-like cells labelled by ASPM that could be the progenitor cells of adult bladder urothelium. ASPM+ urothelial cells are significantly increased after injury by UPEC. In addition, specific transcription factors were found to be associated with urothelial cell differentiation. At the last, a number of interstitial cystitis/bladder pain syndrome-regulating genes were found differentially expressed among different urothelial cell subpopulations. CONCLUSIONS: Our study provides a comprehensive characterization of bladder urothelial cells, which is fundamental to understanding the biology of bladder urothelium and associated bladder disease.

Far-field super-focusing by a feedback-based wavefront shaping method.

Abbe diffraction limit has always been an important subject in conventional far-field focusing and imaging systems, where the resolution of an image is usually limited to 0.5λ/NA. Recently, the studies of the optical super-oscillation lens (SOL) enable us to break the limitation in both theory and practice successfully. Here a genetic algorithm was introduced to design the SOL phase more controllably and precisely obtain much better focusing such as the focal spot with 0.105λ/NA (or 79.0% minification) in the simulation and 65.5% minification in the experimental demonstration. This technique is of great significance in advanced optical lithography or biology microscopy, because it promises non-invasive unlabelled imaging from the far field.

Global expression profiling of metabolic pathway-related lncRNAs in human gastric cancer and the identification of RP11-555H23.1 as a new diagnostic biomarker.

BACKGROUND: Long noncoding RNAs (lncRNAs) have roles in regulating metabolism; however, the global expression profile of metabolic pathway-associated lncRNAs in gastric cancer is unknown. The purpose of our study was to examine metabolic pathway-related lncRNAs in gastric cancer and their possible diagnostic values. METHODS: Differential expression patterns of metabolic pathway-related lncRNAs between gastric cancer and paired nontumor tissues were detected using metabolic pathway-associated lncRNA microarrays. The expression of RP11-555H23.1, one representative metabolic pathway-associated lncRNA, was validated using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The associations between RP11-55H23.1 expression and the clinicopathological features of gastric cancer patients were analyzed. A receiver operating characteristic (ROC) curve was further established. RESULTS: A total of 114 differentially expressed metabolic pathway-associated lncRNAs (fold change >2, P < 0.05) between cancer and nontumor tissues were found (GEO No. GSE96856). Among them, TUG1, RP11-555H23.1, RP1-257I20.13, UGP2, GCSHP3, and XLOC_000889 lncRNAs were downregulated more than sixfold in gastric cancer tissues. In contrast, RP11-605F14.2, TBC1D3P5, BC130595, LINC00475, RP11-19P22.6, BC080653, XLOC_004923, AFAP1-AS1, EPB49, and RP11-296I10.3 lncRNAs were upregulated more than sixfold in gastric cancer tissues. We further demonstrated that RP11-555H23.1 expression was significantly correlated with TNM stage (P = 0.038). The area under the ROC curve (AUC) was 0.65, and the specificity and sensitivity were 62% and 81%, respectively. CONCLUSIONS: Metabolic pathway-associated lncRNAs play an important role in the occurrence of gastric cancer, and metabolic pathway-associated lncRNAs, such as RP11-555H23.1, may represent novel biomarkers of gastric cancer.