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Nanomaterials with unique structures and functions have been widely used in the fields of microelectronics, biology, medicine, and aerospace, etc. With advantages of high resolution and multi functions (e.g., milling, deposition, and implantation), focused ion beam (FIB) technology has been widely developed due to urgent demands for the 3D fabrication of nanomaterials in recent years. In this paper, FIB technology is illustrated in detail, including ion optical systems, operating modes, and combining equipment with other systems. Together with the in situ and real-time monitoring of scanning electron microscopy (SEM) imaging, a FIB-SEM synchronization system achieved 3D controllable fabrication from conductive to semiconductive and insulative nanomaterials. The controllable FIB-SEM processing of conductive nanomaterials with a high precision is studied, especially for the FIB-induced deposition (FIBID) 3D nano-patterning and nano-origami. As for semiconductive nanomaterials, the realization of high resolution and controllability is focused on nano-origami and 3D milling with a high aspect ratio. The parameters of FIB-SEM and its working modes are analyzed and optimized to achieve the high aspect ratio fabrication and 3D reconstruction of insulative nanomaterials. Furthermore, the current challenges and future outlooks are prospected for the 3D controllable processing of flexible insulative materials with high resolution. [ABSTRACT FROM AUTHOR]

Simple Summary: The link between bladder cancer and urinary microbiota has been of high interest, but few studies have shed the light on the concrete urinary species as the potential clinical biomarkers. In this article, we reported the previously ignored urinary species Eubacterium sp. CAG:581 in predicting the occurrence of non-muscle invasive bladder cancer (NMIBC). Excluding the favorable impact of age, sex, smoking, alcohol consumption and other potential contributing factors, we have found Eubacterium sp. CAG:581 has contributed to the development of bladder cancer through activating the extracellular matrix protein 1-matrix metalloproteinase 9 pathway. In the cohort of 406 NMIBC patients and 398 healthy controls, we found that high Eubacterium sp. CAG:581 will correctly distinguish an NMIBC patient from a healthy person by the chance of 79% within 3 years. Collectively, this study manifested that Eubacterium sp. CAG:581 may serve as the promising noninvasive diagnostic biomarker for NMIBC. Background: Increasing evidence points to the urinary microbiota as a possible key susceptibility factor for early-stage bladder cancer (BCa) progression. However, the interpretation of its underlying mechanism is often insufficient, given that various environmental conditions have affected the composition of urinary microbiota. Herein, we sought to rule out confounding factors and clarify how urinary Eubacterium sp. CAG:581 promoted non-muscle invasive bladder cancer (NMIBC) development. Methods: Differentially abundant urinary microbiota of 51 NMIBC patients and 47 healthy controls (as Cohort 1) were first determined by metagenomics analysis. Then, we modeled the coculture of NMIBC organoids with candidate urinary Eubacterium sp. CAG:581 in anaerobic conditions and explored differentially expressed genes of these NMIBC tissues by RNA-Seq. Furthermore, we dissected the mechanisms involved into Eubacterium sp. CAG:581 by inducing extracellular matrix protein 1 (ECM1) and matrix metalloproteinase 9 (MMP9) upregulation. Finally, we used multivariate Cox modeling to investigate the clinical relevance of urinary Eubacterium sp. CAG:581 16S ribosomal RNA (16SrRNA) levels to the prognosis of 406 NMIBC patients (as Cohort 2). Results: Eubacterium sp. CAG:581 infection accelerated the proliferation of NMIBC organoids (p < 0.01); ECM1 and MMP9 were the most upregulated genes induced by the increased colony forming units (CFU) gradient of Eubacterium sp. CAG:581 infection via phosphorylating ERK1/2 in NMIBC organoids of Cohort 1. Excluding the favorable impact of potential contributing factors, the ROC curve of Cohort 2 manifested its 3-year AUC value as 0.79 and the cut-off point of Eubacterium sp. CAG:581 16SrRNA as 10.3 (delta CT value). Conclusion: Our evidence suggests that urinary Eubacterium sp. CAG:581 promoted NMIBC progression through the ECM1/MMP9 pathway, which may serve as the promising noninvasive diagnostic biomarker for NMIBC. [ABSTRACT FROM AUTHOR]

(1) Background: The purpose of this study was to evaluate the effect of gene polymorphisms on prothrombin time (PT) and activated partial thromboplastin time (APTT) in a healthy Chinese population. (2) Methods: A total of 403 healthy volunteers from a series of novel oral anticoagulants (NOACs) bioequivalence trials in China were included. Coagulation tests for PT and APTT were performed in the central lab at Peking University First Hospital. Whole-exome sequencing (WES) and genome-wide association analysis were performed. (3) Results: In the correlation analysis of PT, 105 SNPs from 84 genes reached the genome-wide significance threshold (p < 1 × 10−5). Zinc Finger Protein 594 (ZNF594) rs184838268 (p = 4.50 × 10−19) was most significantly related to PT, and Actinin Alpha 1 (ACTN1) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (AURKB), Complement C5(C5), Clock Circadian Regulator (CLOCK), and Histone Deacetylase 9(HDAC9) were detected in our dataset (p < 1 × 10−5). PiggyBac Transposable Element Derived 2(PGBD2) rs75935520 (p = 4.49 × 10−6), Bromodomain Adjacent To Zinc Finger Domain 2A(BAZ2A) rs199970765 (p = 5.69 × 10−6) and Protogenin (PRTG) rs80064850 (p = 8.69 × 10−6) were significantly correlated with APTT (p < 1 × 10−5). The heritability values of PT and APTT were 0.83 and 0.64, respectively; (4) Conclusion: The PT and APTT of healthy populations are affected by genetic polymorphisms. ZNF594 and ACTN1 variants could be novel genetic markers of PT, while PRTG polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation. [ABSTRACT FROM AUTHOR]