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RNA binding proteins (RBPs) regulate nearly all post-transcriptional processes within cells. To fully understand RBP function, it is essential to identify their in vivo targets. Standard techniques for profiling RBP targets, such as crosslinking immunoprecipitation (CLIP) and its variants, are limited or suboptimal in some situations, e.g. when compatible antibodies are not available and when dealing with small cell populations such as neuronal subtypes and primary stem cells. This review summarizes and compares several genetic approaches recently designed to identify RBP targets in such circumstances. TRIBE (targets of RNA binding proteins identified by editing), RNA tagging, and STAMP (surveying targets by APOBEC-mediated profiling) are new genetic tools useful for the study of post-transcriptional regulation and RBP identification. We describe the underlying RNA base editing technology, recent applications, and therapeutic implications.

Arias intensity (IA), as an important seismic parameter, which contains the information of amplitude, frequencies, and duration of ground motion, plays a crucial role in characterizing seismic hazard such as earthquake-induced landslides. In this article, we conducted probabilistic seismic hazard analysis (PSHA) based on IA in China’s north–south seismic belt. We adopted the seismic sources and seismicity parameters used in the fifth generation of the Seismic Ground Motion Parameter Zoning Map of China, and two ground-motion model of IA. The results show that the values of IA are greater than 0.11 m/s in most regions of the north–south seismic belt. The provincial capital cities and most prefecture-level cities in the seismic zone are located in the region with IA-values greater than 0.32 m/s. The values of IA are above 0.54 m/s in the region around the main fault zone. This means that the north–south seismic belt is prone to extremely high-seismic hazard, particularly earthquake-induced landslides. Therefore, it is important to strengthen the evaluation and prevention of earthquake-induced landslides in this area. As we have found significant differences in the values of IA calculated from different ground-motion model, it is necessary to study the ground-motion model of IA for the western geological environment of China. In addition, the PSHA based on IA gives more consideration to the influence of large earthquakes than that based on peak ground acceleration. Therefore, IA plays an important role in seismic design of major engineering projects. The results of this article are of great scientific significance for understanding the seismic hazard of the north–south seismic belt.

The temporal distribution of earthquakes provides important basis for earthquake prediction and seismic hazard analysis. The relatively limited records of strong earthquakes have often made it difficult to study the temporal distribution models of regional strong earthquakes. However, there are hundreds of years of complete strong earthquake records in North China Seismic Zone, providing abundant basic data for studying temporal distribution models. Using the data of M ≥ 6.5 earthquakes in North China as inputs, this paper estimates the model parameters using the maximum likelihood method with exponential, Gamma, Weibull, Lognormal and Brownian passage time (BPT) distributions as target models. The optimal model for describing the temporal distribution of earthquakes is determined according to Akaike information criterion (AIC), determination coefficient R2 and Kolmogorov-Smirnov test (K-S test). The results show that Lognormal and BPT models perform better in describing the temporal distribution of strong earthquakes in North China. The mean recurrence periods of strong earthquakes (M ≥ 6.5) calculated based on these two models are 8.1 years and 13.2 years, respectively. In addition, we used the likelihood profile method to estimate the uncertainty of model parameters. For the BPT model, the mean and 95% confidence interval of recurrence interval µ is 13.2 (8.9–19.1) years, and the mean and 95% confidence interval of α is 1.29 (1.0-1.78). For the Lognormal model, the mean value and 95% confidence interval of v is 2.09 (1.68–2.49), the mean value exp (v) corresponding to earthquake recurrence interval is 8.1 (5.4–12.1) years. In this study, we also calculated the occurrence probability of M ≥ 6.5 earthquakes in North China Seismic Zone in the future, and found that the probability and 95% confidence interval in the next 10 years based on the BPT model is 35.3% (26.8%-44.9%); the mean value and 95% confidence interval of earthquake occurrence probability based on the Lognormal distribution is 35.4% (22.9%-49.7%); the mean probability and 95% confidence interval based on the Poisson model is 53.1% (41.1%-64%). The results of this study may provide important reference for temporal distribution model selection and earthquake recurrence period calculation in future seismic hazard analysis in North China.

Earthquakes are among the most devastating natural disasters in China, causing serious casualties and property losses. To effectively reduce catastrophic risk, it is important to establish an earthquake catastrophe insurance system based on the earthquake catastrophe model, of which seismic hazard analysis is a main module. Probabilistic seismic-hazard analysis uses the potential source model, seismicity model, and ground-motion attenuation model, as well as the probability method to obtain the seismic hazard value of a given point. However, because the influence of a single seismic event is required when the earthquake catastrophe model is used for risk analysis, a series of single events needs to be generated according to the potential source model so as to calculate the influence of each event on the given point. In this study, based on the seismicity model (potential sources and their seismicity parameters) used in compiling the fifth generation of Seismic Ground Motion Parameter Zoning Map of China, we use the Monte Carlo method to simulate seismic events conforming to temporal, spatial, and intensity distribution of China’s seismic activities. In the simulation process, we follow the Poisson distribution in occurrence time and the Gutenberg–Richter law in magnitude distribution, and we use potential sources and earthquake occurrence rates to describe spatial distribution. The simulated seismic events include the following parameters: date (year, month, and day), location (longitude and latitude), depth, magnitude, and attitude of seismogenic faults. The simulated seismic event set can support earthquake risk analysis in the earthquake catastrophe model and has been applied in the earthquake catastrophe model of China.

Background A variety of diabetes self-management instruments have been developed but few of them consist of the preparedness for diabetes self-management behavior. The novel psychometric evaluation tool “the LMC Skills, Confidence & Preparedness Index (SCPI)” measures three key aspects of a patient’s diabetes self-management: knowledge of the skill, confidence in being able to perform skill and preparedness to implement the skill. The objective of this study was to translate, adapt and validate the SCPI for use in Chinese adult patients with type 2 diabetes. Methods This study followed the guideline recommended by the American Academy of Orthopaedic Surgeons Evidence Based Medicine Committee (AAOS) to indigenize the scale. Forward and back translation, and cross-cultural language debugging were completed according to the recommended steps. A convenience sample of Chinese patients with type 2 diabetes (n = 375) were recruited from a university-affiliated hospital in Shanghai. The validity (criterion, discriminant validity, and construct validity), reliability (internal consistency and test–retest reliability) and the interpretability of the instrument were examined. The content validity was calculated by experts’ evaluation. Results The Chinese version of SCPI (C-SCPI) has good internal consistency with a Cronbach’s alpha of 0.92. The ceiling effects of the preparedness subscales is 21%. The criterion validity of three dimensions of C-SCPI was established with significantly moderate correlations between the DKT, DES-SF and SDSCA (p 2/df = 2.775, RMSEA = 0.069, CFI = 0.903, GFI = 0.873, TLI = 0.889, IFI = 0.904. The test–retest reliability coefficient was 0.61 (p Conclusion We established a Chinese version of SCPI through translation and cross-cultural adaptation. The C-SCPI is reliable and valid for assessment of the level of self-management in Chinese patients with type 2 diabetes.

An earthquake catalog based on a unified magnitude scale is an important prerequisite for analyses of seismic activities and seismic hazards. To unify the magnitude scales of earthquakes in China’s seas and neighboring regions, we developed conversion relationships between surface- and body-wave magnitudes and the global centroid moment tensor (GCMT) and National Research Institute for Earth Science and Disaster Resilience (NIED) moment magnitudes for shallow and intermediate- and deep-focus earthquakes in China’s seas and adjacent areas. We employed data collected by the Chinese Earthquake Network Center, GCMT, and NIED for earthquakes of magnitude 4.5 and higher in China’s seas and neighboring regions from 1976 to 2018. We used the linear least squares regression method and the orthogonal regression method to fit the seismic data under different magnitude ranges and different focal depth ranges. The results provided empirical formulas to unify magnitude scales for the earthquakes in China’s seas and neighboring regions and also provided an important basis for seismic catalog integrity analyses and seismic activity studies for this area. The results are significant for seismic hazard analyses, seismic zoning, and mid- and long-term forecast analyses of seismic activities in the area.

In this study, we use a spatially smoothed seismicity procedure for seismic hazard analysis in North China seismic zone by establishing four spatially smoothed seismicity models according to the seismic catalogs of North China and calculating peak ground acceleration (PGA) values with 10% probability of exceedance in 50 years. The results show considerable differences between seismic hazards based on different models in certain areas, which is attributable to disparities in the seismicity levels of the four seismic models in those areas. In general, seismic hazard based on different models can be used as reference to evaluate uncertainty. In this paper, we also compare the mean PGA based on four spatially smoothed seismicity models with another PGA calculated using the zoning method based on surface seismic sources adopted for generating the Seismic Ground Motion Parameter Zonation Map of China, and find that the results of the two methods are largely similar, both of which can reflect the seismic hazard level of North China. However, there are differences at certain points, which are because the zoning approach adopts the same earthquake occurrence rate in the seismic source, while the spatially smoothed seismicity approach has different occurrence rates at different points. The discrepancies between the two can be attributed to differences in the principles adopted when potential seismic sources are classified. In particular, the PGA values of Beijing with 10% probability of exceedance in 50 years is 177.0cm/s2, 214.2 cm/s2, 252.8 cm/s2, and 187.5 cm/s2 in four spatial seismicity models, respectively. These PGA values are very important for evaluating the uncertainty of seismic hazard in Beijing. This study is an attempt to perform seismic hazard analysis using spatially smoothed seismicity models in China and recommends using this approach for areas where seismic sources are not clearly identified.

RNA translation is tightly regulated to ensure proper protein expression in cells and tissues. Translation is often assayed with biochemical assays such as ribosome profiling and TRAP, which are effective in many contexts. These assays are however not ideal with limiting amounts of biological material when it can be difficult or even impossible to make an extract with sufficient signal or sufficient signal:noise. Because of our interest in translational regulation within the few Drosophila adult circadian neurons, we fused the ADAR catalytic domain (ADARcd) to several small subunit ribosomal proteins and assayed mRNA editing in Drosophila S2 cells. The strategy is named RiboTRIBE and is analogous to a recently published APOBEC-based method. The list of RiboTRIBE-edited transcripts overlaps well with ribosome profiling targets, especially with more highly ranked targets. There is also an enriched number of editing sites in ribosome-associated mRNA comparing to total mRNA, indicating that editing occurs preferentially on polyribosome-associated transcripts. The use of cycloheximide to freeze translating ribosomes causes a substantial increase in the number of RiboTRIBE targets, which is decreased by pretreating cells with the chain terminating drug puromycin. NOTE: Additional experiments performed after first submitting this manuscript to BioRxiv estimate that less than 5% of Rps28b-ADAR is ribosome-associated. This is because the vast majority of the fusion protein sediments at the top of a polyribosome gradient. We therefore suggest that most editing reported in the manuscript is not catalyzed by ribosome-associated ADAR (10/2/2021).

Additional file 1. Process of cross-cultural adaptation & General information of experts & Modified content after interviewing.

We used a relatively new method, HyperTRIBE, to identify in vivo RNA targets of the translation inhibitor 4E-BP., 4E-BP (eIF4E-BP) represses translation initiation by binding to the 5′ cap–binding protein eIF4E and inhibiting its activity. Although 4E-BP has been shown to be important in growth control, stress response, cancer, neuronal activity, and mammalian circadian rhythms, it is not understood how it preferentially represses a subset of mRNAs. We successfully used HyperTRIBE (targets of RNA binding proteins identified by editing) to identify in vivo 4E-BP mRNA targets in both Drosophila and mammals under conditions known to activate 4E-BP. The protein associates with specific mRNAs, and ribosome profiling data show that mTOR inhibition changes the translational efficiency of 4E-BP TRIBE targets more substantially compared to nontargets. In both systems, these targets have specific motifs and are enriched in translation-related pathways, which correlate well with the known activity of 4E-BP and suggest that it modulates the binding specificity of eIF4E and contributes to mTOR translational specificity.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein which forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases. Despite our understanding that TDP-43 is essential for many aspects of RNA metabolism, it remains obscure how TDP-43 dysfunction contributes to neurodegeneration. Interestingly, altered neuronal dendritic morphology is a common theme among several neurological disorders and is thought to precede neurodegeneration. We previously found that both TDP-43 overexpression (OE) and knockdown (KD) result in reduced dendritic branching of cortical neurons. In this study, we used TRIBE (targets of RNA-binding proteins identified by editing) as an approach to identify signaling pathways that regulate dendritic branching downstream of TDP-43. We found that TDP-43 RNA targets are enriched for pathways that signal to the CREB transcription factor. We further found that TDP-43 dysfunction inhibits CREB activation and CREB transcriptional output, and restoring CREB signaling rescues defects in dendritic branching. Finally, we demonstrate, using RNA sequencing, that TDP-43 OE and KD cause similar changes in the abundance of specific messenger RNAs, consistent with their ability to produce similar morphological defects. Our data therefore provide a mechanism by which TDP-43 dysfunction interferes with dendritic branching, and may define pathways for therapeutic intervention in neurodegenerative diseases.

RNA-binding proteins (RBPs) accompany RNA from birth to death, affecting RNA biogenesis and functions. Identifying RBP-RNA interactions is essential to understanding their complex roles in different cellular processes. However, detecting in vivo RNA targets of RBPs, especially in a small number of discrete cells, has been a technically challenging task. We previously developed a novel technique called TRIBE (targets of RNA-binding proteins identified by editing) to overcome this problem. TRIBE expresses a fusion protein consisting of a queried RBP and the catalytic domain of the RNA-editing enzyme ADAR (adenosine deaminase acting on RNA) (ADARcd), which marks target RNA transcripts by converting adenosine to inosine near the RBP binding sites. These marks can be subsequently identified via high-throughput sequencing. In spite of its usefulness, TRIBE is constrained by a low editing efficiency and editing-sequence bias from the ADARcd. Therefore, we developed HyperTRIBE by incorporating a previously characterized hyperactive mutation, E488Q, into the ADARcd. This strategy increases the editing efficiency and reduces sequence bias, which markedly increases the sensitivity of this technique without sacrificing specificity. HyperTRIBE provides a more powerful strategy for identifying RNA targets of RBPs with an easy experimental and computational protocol at low cost, that can be performed not only in flies, but also in mammals. The HyperTRIBE experimental protocol described below can be carried out in cultured Drosophila S2 cells in 1 week, using tools available in a common molecular biology laboratory; the computational analysis requires 3 more days.

Disaster preparedness is critical for reducing potential impact. This paper contributes to current knowledge of disaster preparedness using representative national sample data from China, which faces high earthquake risks in many areas of the country. The adoption of earthquake preparedness activities by the general public, including five indicators of material preparedness and five indicators of awareness preparedness, were surveyed and 3245 respondents from all 31 provinces of Mainland China participated in the survey. Linear regression models and logit regression models were used to analyze the effects of potential influencing factors. Overall, the preparedness levels are not satisfied, with a material preparation score of 3.02 (1–5), and awareness preparation score of 2.79 (1–5), nationally. Meanwhile, residents from western China, which has higher earthquake risk, have higher degrees of preparedness. The concern for disaster risk reduction (DRR) and the concern for building safety and participation in public affairs are consistent positive predictors of both material and awareness preparedness. The demographic and socioeconomic variables' effects, such as gender, age, education, income, urban/rural division, and building size, vary according to different preparedness activities. Finally, the paper concludes with a discussion of the theoretical contribution and potential implementation.