Accurate and systematic transcriptome-wide detection of 5-methylcytosine (m
C) has proved challenging, and there are conflicting views about the prevalence of this modification in mRNAs. Here we ...report an experimental and computational framework that robustly identified mRNA m
C sites and determined sequence motifs and structural features associated with the modification using a set of high-confidence sites. We developed a quantitative atlas of RNA m
C sites in human and mouse tissues based on our framework. In a given tissue, we typically identified several hundred exonic m
C sites. About 62-70% of the sites had low methylation levels (<20% methylation), while 8-10% of the sites were moderately or highly methylated (>40% methylation). Cross-species analysis revealed that species, rather than tissue type, was the primary determinant of methylation levels, indicating strong cis-directed regulation of RNA methylation. Combined, these data provide a valuable resource for identifying the regulation and functions of RNA methylation.
Medical sealant devices for in vivo hemostasis are far from satisfactory in the aged society. A major challenge is effective integration of quick hemorrhage control of the increased anticoagulated ...patients, high safety, and facile accessibility. Here, a well‐defined ammonolysis‐based Tetra‐PEG hydrogel sealant is developed with rapid gelation speed, strong tissue adhesion, and high mechanical strength. Introduction of cyclized succinyl ester groups into a hydrogel matrix endows the sealant with fast degradable and controllably dissolvable properties. The hydrogel possesses outstanding hemostatic capabilities even under the anticoagulated conditions while displaying excellent biocompatibility and feasibility. These results reveal that the optimized hydrogel may be a facile, effective, and safe sealant for hemorrhage control in vivo.
A PEG sealant with fast and controllable degradation properties is constructed for in vivo visceral organ hemostasis, which possesses high hemostatic efficacy even under anticoagulated situations and which, even more remarkably, does not hinder the tissue healing and cause side effects.
Tissue engineering is a promising strategy for the repair and regeneration of damaged tissues or organs. Biomaterials are one of the most important components in tissue engineering. Recently, ...magnetic hydrogels, which are fabricated using iron oxide-based particles and different types of hydrogel matrices, are becoming more and more attractive in biomedical applications by taking advantage of their biocompatibility, controlled architectures, and smart response to magnetic field remotely. In this literature review, the aim is to summarize the current development of magnetically sensitive smart hydrogels in tissue engineering, which is of great importance but has not yet been comprehensively viewed.
Adenosine-to-inosine (A-to-I) RNA editing regulates miRNA biogenesis and function. To date, fewer than 160 miRNA editing sites have been identified. Here, we present a quantitative atlas of miRNA ...A-to-I editing through the profiling of 201 pri-miRNA samples and 4694 mature miRNA samples in human, mouse, and
We identified 4162 sites present in ∼80% of the pri-miRNAs and 574 sites in mature miRNAs. miRNA editing is prevalent in many tissue types in human. However, high-level editing is mostly found in neuronal tissues in mouse and
Interestingly, the edited miRNAs in neuronal and non-neuronal tissues in human gain two distinct sets of new targets, which are significantly associated with cognitive and organ developmental functions, respectively. Furthermore, we reveal that miRNA editing profoundly affects asymmetric strand selection. Altogether, these data provide insight into the impact of RNA editing on miRNA biology and suggest that miRNA editing has recently gained non-neuronal functions in human.
Abstract
Advances in sequencing technologies have empowered epitranscriptomic profiling at the single-base resolution. Putative RNA modification sites identified from a single high-throughput ...experiment may contain one type of modification deposited by different writers or different types of modifications, along with false positive results because of the challenge of distinguishing signals from noise. However, current tools are insufficient for subtyping, visualization, and denoising these signals. Here, we present iMVP, which is an interactive framework for epitranscriptomic analysis with a nonlinear dimension reduction technique and density-based partition. As exemplified by the analysis of mRNA m
5
C and ModTect variant data, we show that iMVP allows the identification of previously unknown RNA modification motifs and writers and the discovery of false positives that are undetectable by traditional methods. Using putative m
6
A/m
6
Am sites called from 8 profiling approaches, we illustrate that iMVP enables comprehensive comparison of different approaches and advances our understanding of the difference and pattern of true positives and artifacts in these methods. Finally, we demonstrate the ability of iMVP to analyze an extremely large human A-to-I editing dataset that was previously unmanageable. Our work provides a general framework for the visualization and interpretation of epitranscriptomic data.
Abstract
m
5
C is one of the longest-known RNA modifications, however, its developmental dynamics, functions, and evolution in mRNAs remain largely unknown. Here, we generate quantitative mRNA m
5
C ...maps at different stages of development in 6 vertebrate and invertebrate species and find convergent and unexpected massive methylation of maternal mRNAs mediated by NSUN2 and NSUN6. Using
Drosophila
as a model, we reveal that embryos lacking maternal mRNA m
5
C undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA m
5
C. From invertebrates to the lineage leading to humans, two waves of m
5
C regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated m
5
C sites at the 5' end of the mRNAs, accompanied by the emergence of more structured 5'UTR regions; humans gain thousands of trans-directed NSUN6-mediated m
5
C sites enriched in genes regulating the mitotic cell cycle. Collectively, our studies highlight the existence and regulatory innovations of a mechanism of early embryonic development and provide key resources for elucidating the role of mRNA m
5
C in biology and disease.
Infected nonunion of tibia and femur are common in clinical practice, however, the treatment of these diseases has still been a challenge for orthopaedic surgeons. Ilizarov methods can eradicate ...infection, compensate bone defects and promote the bone union through progressive bone histogenesis. The objective of this systematic review was to review current available studies reporting on Ilizarov methods in the treatment of infected nonunion of tibia and femur, and to perform meta-analysis of bone and functional results and complications to evaluate the efficacy of Ilizarov methods.
A comprehensive literature search was performed from the SCI, PubMed, Cochrane Library; and Embase between January 1995 and August 2015. Some major data were statistically analyzed using weighted means based on the sample size in each study by SPSS 13.0, including number of patients, mean age, mean previous surgical procedures, mean bone defects, mean length of follow-up, bone union, complications per patient, external fixation time, and external fixation index(EFI). Bone results (excellent, good, fair and poor rate), functional results (excellent, good, fair and poor rate) and complications were analyzed by Stata 9.0.
A total of 590 patients from 24 studies were included in this systematic review. The average of bone union rate was 97.26% in all included studies. The poor rate in bone results and functional results was 8% (95%CI, 0.04-0.12; I2 = 44.1%, P = 0.065) and 10% (95%CI, 0.05-0.14; I2 = 34.7%, P = 0.121) in patients with infected nonunion of tibia and femur treated by Ilizarov methods. The rate of refracture, malunion, infectious recurrence, knee stiffness, amputation, limb edema and peroneal nerve palsy was respectively 4%, 7%, 5%, 12%, 4%, 13% and 13%.
Our systematic review showed that the patients with infected nonunion of tibia and femur treated by Ilizarov methods had a low rate of poor bone and functional results. Therefore, Ilizarov methods may be a good choice for the treatment of infected nonunion of tibia and femur.
Rapid and effective hemostasis is of great importance to improve the quality of treatment and save lives in emergency, surgical practice, civilian, and military settings. Traditional hemostatic ...materials such as tourniquets, gauze, bandages, and sponges have shown limited efficacy in the management of uncontrollable bleeding, resulting in widespread interest in the development of novel hemostatic materials and techniques. Benefiting from biocompatibility, degradability, injectability, tunable mechanical properties, and potential abilities to promote coagulation, wound healing, and anti-infection, hydrogel-based biomaterials, especially those on the basis of natural polysaccharides and proteins, have been increasingly explored in preclinical studies over the past few years. Despite the exciting research progress and initial commercial development of several hemostatic hydrogels, there is still a significant distance from the desired hemostatic effect applicable to clinical treatment. In this review, after elucidating the process of biological hemostasis, the latest progress of hydrogel biomaterials engineered from natural polysaccharides and proteins for hemostasis is discussed on the basis of comprehensive literature review. We have focused on the preparation strategies, physicochemical properties, hemostatic and wound-healing abilities of these novel biomaterials, and highlighted the challenges that needed to be addressed to achieve the transformation of laboratory research into clinical practice, and finally presented future research directions in this area.
The optimal treatment modality for upper lumbar disc herniation remains unclear. Herein, we compared the clinical efficacy and application value of minimally invasive transforaminal lumbar interbody ...fusion (MIS-TLIF) and transforaminal lumbar interbody fusion (TLIF) for upper lumbar disc herniation. We aimed to provide new evidence to guide surgical decisions for treating this condition.
We retrospectively analyzed the clinical data of 81 patients with upper lumbar disc herniation admitted between January 2017 and July 2018, including 41 and 40 patients who underwent MIS-TLIF and TLIF, respectively. Demographic characteristics, preoperative functional scores, perioperative indicators, and postoperative complications were compared. We performed consecutive comparisons of visual analog scale (VAS) scores of the lumbar and leg regions, Oswestry disability index (ODI), Japanese Orthopaedic Association scores (JOA), and MacNab scores at the final follow-up, to assess clinical outcomes 5 years postoperatively.
VAS scores of the back and legs were significantly lower in the MIS-TLIF than the TLIF group at 3 months and 1 year postoperatively (P < 0.05). Intraoperative bleeding and postoperative hospitalization time were significantly lower, and the time to return to work/normal life was shorter in the MIS-TLIF than in the TLIF group (P < 0.05). The differences in JOA scores and ODI scores between the two groups at 3 months, 1 year, and 3 years postoperatively were statistically significant (P < 0.05).
The early clinical efficacy of MIS-TLIF was superior to that of TLIF, but no differences were found in mid-term clinical efficacy. Further, MIS-TLIF has the advantages of fewer medical injuries, shorter hospitalization times, and faster postoperative functional recovery.
The treatment of bone tissue defects remains a complicated clinical challenge. Recently, the bone tissue engineering (BTE) technology has become an important therapeutic approach for bone defect ...repair. Researchers have improved the scaffolds, cells, and bioactive factors used in BTE through various existing bone repair material preparation strategies. However, due to insufficient vascularization, inadequate degradation, and fibrous wrapping, most BTE scaffolds impede new bone ingrowth and the reconstruction of grid-like connections in the middle and late stages of bone repair. These non-degradable scaffolds become isolated and disordered like independent "isolated islands", which leads to the failure of osteogenesis. Consequently, we hypothesized that the "island effect" prevents successful bone repair. Accordingly, we proposed a new concept of scaffold modification-osteogenesis requires a bone temporary shelter (also referred to as the empty shell osteogenesis concept). Based on this concept, we consider that designing hollow structural scaffolds is the key to mitigating the "isolated island" effect and enabling optimal bone regeneration and reconstruction.
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