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Aim: This study aimed to investigate the biological functions of miRNAs in hepatobiliary tumors as the focus of targeted therapy research. Background: Hepatobiliary tumors are among the leading causes of cancer-related deaths worldwide. Many microRNAs (miRNAs) play an important regulatory role in tumor progression. Our study aims to explore some biologically functional miRNAs from different datasets of hepatobiliary tumors for disease diagnosis or treatment. Objective: In this study, we tried to filter out differentially expressed miRNAs in different tumor datasets from the GEO database. Methods: In this study, we first perform analyses in different GEO data sets. After taking the intersection, the initial scope is limited to several differential RNAs. Then, combined with the existing research results from Kaplan-Meier survival analysis and literature, the candidate molecule was finally identified to be studied. Furthermore, the biological characteristics analysis of the candidate molecule was performed on the basis of Cancermirnome online tool, including expression levels in tumors, KEGG and GO analysis, ROC analysis, and target gene prediction. Furthermore, the effect of the candidate molecule on the biological functions of liver cancer was verified by in vitro assay. Results: The preliminary analysis of bioinformatics shows that 16 differentially expressed miRNAs may play an important role in HCC or ICC. Ultimately, we identified miRNA-99a-5p as the only molecule to study. The results showed that miRNA-99a-5p is abnormally expressed in many tumors, and in liver cancer, its level of expression in tumor tissue is significantly lower than that in normal tissue. Then, the KEGG and GO analysis found that it functions in multiple pathways. At the same time, the ROC analysis found that it showed great potential for prognostic prediction in HCC and we also predicted that RUNDC3B is the most likely target to which it binds. Finally, the experimental results of overexpression and knockdown confirmed that miRNA-99a-5p could inhibit cell proliferation in HCC, which also suggested that it may be an important tumor suppressor in HCC. Conclusion: MiRNA-99a-5p was negatively correlated with HCC progression and could act as a novel therapeutic target for HCC.

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation^{1,2}. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole^3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of 8.4_{-1.1}^{+0.5} Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow., 50 pages, 18 figures, 3 tables, author's version of the paper published in Nature

Despite advances in our understanding of low luminosity active galactic nuclei (LLAGNs), the fundamental details about the mechanisms of radiation and flare/outburst in hot accretion flow are still largely missing. We have systematically analyzed the archival Chandra and NuSTAR X-ray data of the nearby LLAGN M81*, whose $L_{\rm bol}\sim 10^{-5} L_{\rm Edd}$. Through a detailed study of X-ray light curve and spectral properties, we find that the X-ray continuum emission of the power-law shape more likely originates from inverse Compton scattering within the hot accretion flow. In contrast to Sgr A*, flares are rare in M81*. Low-amplitude variation can only be observed in soft X-ray band (amplitude usually $\lesssim 2$). Several simple models are tested, including sinusoidal-like and quasi-periodical. Based on a comparison of the dramatic differences of flare properties among Sgr A*, M31* and M81*, we find that, when the differences in both the accretion rate and the black hole mass are considered, the flares in LLAGNs can be understood universally in a magneto-hydrodynamical model., 11 pages, 8 figures, and 4 tables. Accepted to MNRAS

A parametric study of ramp-induced planar shock-wave/turbulent-boundary-layer interactions (SBLIs) is carried out at hypersonic conditions (Mach number 6.0) by means of numerical simulation of the Reynolds-averaged Navier–Stokes (RANS) equations, with the eventual goal of establishing wall temperature and Reynolds number effects. Comparison with available experimental data shows that RANS is capable of predicting the main features of hypersonic oblique SBLI, namely, typical size and distribution of the wall-surface pressure, and heat transfer. A large number of flow cases, at low ([Formula: see text]) and high Reynolds number ([Formula: see text]), were computed to examine the scaling of the heat transfer over a wide range of wall temperatures. As expected, the interaction zone of hypersonic ramp-induced SBLI is reduced as the wall is cooled. A simple power law for heat transfer originally introduced by Back and Cuffel (AIAA Journal, Vol. 8, No. 10, 1970, pp. 1871–1873) is here considered to account for hypersonic ramp-induced SBLI, which is found to successfully collapse the data to the distributions obtained for supersonic, cold/hot interactions.

Objective: To observe the clinical effect of different frequencies of transcutaneous electrical acupoint stimulation in treating postpartum pelvic girdle pain and promoting postpartum rehabilitation. Methods: From January to September 2022, 300 patients with pelvic girdle pain after spontaneous delivery in a hospital in Shaanxi Province were selected and randomly divided into three groups, low frequency, high frequency, and alternating frequency, with 100 cases in each group. In addition to routine postpartum care and psychological counseling, the three groups received transcutaneous electrical acupoint stimulation at low-frequency (2 Hz,) high-frequency (100 Hz), and alternating frequency (2/100 Hz), respectively. The differences in initial pain, pain scores before and after treatment, satisfaction with analgesic effect, and postpartum rehabilitation effect were evaluated among the three groups of patients. Results: There was a significant correlation between maternal age and postpartum pelvic girdle pain (P < 0.001), but no correlation was observed between newborn birth weight and postpartum pelvic girdle pain (P > 0.05). After 1d/2d of treatment, the pain scores and rehabilitation effect of patients in the alternating-frequency group and low-frequency group were significantly better than those in the high-frequency group, and the postpartum curative effect of patients in the alternating-frequency group was the best, followed by the low-frequency group, and the high-frequency group; the differences were statistically significant (P < 0.001). Among the three groups, the alternating-frequency group had the highest satisfaction with the analgesic effect and the highest rate of selecting the same analgesic regimen the next time; the differences were statistically significant (P < 0.001). Conclusion: Transcutaneous electrical acupoint stimulation at different frequencies is safe and effective in treating postpartum pelvic girdle pain and beneficial to postpartum rehabilitation. Sparse-dense wave stimulation is effective in treating postpartum pelvic girdle pain. It has the best effect in promoting postpartum rehabilitation and the highest patient satisfaction. Therefore, its application in clinical practice is highly recommended.

Highly asymmetric bimetal nanostructures, such as Au-Pt nanorings and Au-Ag nanoplates possess superior plasmonic properties owing to various synergistic effects between different components and diversified morphologies. Herein, we report a controllable growth of asymmetric Pt-Au nanoplates and Au@Pt nanorings with excellent photothermal conversion efficiency. Hexagonal Au nanoplates are used as templates, which is achieved through a transformation reaction from Au nanotriangles. Pt-Au nanoplates is prepared by a site-selective growth of Pt on the rim of obtained hexagonal Au nanoplates. Subsequently, Pt nanorings is obtained by a selective etching of Au, and a regrowth of Au on the Pt nanorings leads to bimetallic Au@Pt nanorings. The evolution of extinction spectra during the whole process is carefully studied. Under irradiation by 1064 nm laser located in the second near-infrared bio-window, the Pt-Au nanoplates exhibit excellent photothermal conversion, better than that of initial Au nanotriangles and hexagonal Au nanoplates with same mass concentration. The improvement of photothermal effect can be ascribed to the strong surface plasmon resonances and coupling between Au and Pt.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a high propensity for invasion and a high incidence of lymph node metastasis. Systemic chemotherapy is considered the primary treatment for patients with TNBC; however, immune checkpoint inhibitors in addition to chemotherapy have been associated with better outcomes. Sintilimab, an anti-PD-1 antibody, was developed in China. Herein, the authors report a 49-year-old woman diagnosed with TNBC with extensive lung and sternal metastases. Treatment with sintilimab plus paclitaxel and carboplatin was found highly effective after failure of first-line chemotherapy. This combinational therapy can be considered for the treatment of TNBC after necessary investigations and clinical trials.

This study was conducted with the purpose of understanding the link between corporate social responsibility (CSR) and employee green behavior. Particularly, we explored the mediating role of supervisor-subordinate guanxi in this relationship. Participants were 327 part-time Master of Business Administration students at three universities in China, who completed a survey. Structural equation modeling was used to test the hypotheses. Results revealed that there was a positive and significant relationship between employees' perceived CSR and their green behavior, and that supervisor-subordinate guanxi partially mediated this relationship. This study extends research on the social outcomes of CSR by shedding new light on the psychological mechanisms connecting it with employee green behavior. The findings will help managers of organizations to better understand how CSR facilitates employee green behavior.

The purpose of this study is to propose a new method to achieve pattern generation from garment sample without damage. The non-contact three-dimensional (3D) scanner was employed to get the point cloud data of garment samples. The Bowyer-Watson algorithm was used to implement Delaunay triangulation for surface reconstruction. The finite element (FE) approach was employed to achieve the consideration of the fabric properties in surface development. The proposed method was demonstrated to effectively realize the pattern generation of 3D sample clothes with fabric properties without damaging the garment samples, and to be suitable for different clothing styles and fabrics. Compared with traditional methods, the proposed method has higher accuracy (2.21% higher on average) and better stability.

The automatic recognition of garment flat information has been widely researched through computer vision. However, the unapparent visual feature and low recognition accuracy pose serious challenges to the application. Herein, inspired by multi-object instance segmentation, the method of mask region convolutional neural network (Mask R-CNN) for garment flat multi-component is proposed in this paper. The steps include feature enhancement, attribute annotation, feature extraction, and bounding box regression and recognition. First, the Laplacian was employed to enhance the image feature, and the Polygon annotated component attributes to reduce the interaction interference. Next, the ResNet was applied to realize identity mapping to characterize redundant information of components. Finally, the feature map was entered into two branches to achieve bounding box regression and recognition. The results demonstrated that the proposed method could realize multi-component recognition effectively. Compared with the unenhanced feature, the mAP increased by 2.27%, reaching 97.87%, and the average F1 was 0.958. Compared to VGGNet and MobileNet, the ResNet backbone used for Mask R-CNN could improve the mAP by 11.55%. Mask R-CNN was more robust than the state-of-the-art methods and more suitable for garment flat multi-component recognition.

The growth of regional plans in China since the new millennium has raised debates regarding the recentralization of the state in response to the crisis of urban entrepreneurialism. The Yangtze River Delta (YRD) region is a case in point for exploration. As the first regional plan of its kind, orchestrated over the YRD, two additional plans have been formulated for this region in the subsequent years. By analyzing the recurrent regional plan experiments in the YRD, this study identified two dominant features that characterized the current regional plan trend in China. The first is the special attention paid to the positioning of the regional territory in the national and international context. The second is the importance attached to the national policy delivery in multilevel government systems. This case study illustrates that the rise of regional plans made by the state does not indicate a departure from entrepreneurial governance. Instead, it represents a “nationalized” YRD entrepreneurial strategy, whereby the national aspirations are regionalized around the YRD. In addition, it manifests recurrent experiments for a governance fix by the state to regulate municipal developments via regional plans without fundamental structural reforms. Through regional plans, the state manages to govern the cities with strategic significance.

Twin proximal support vector regression is a new regression machine designed by using twin support vector machine and proximal support vector regression. In this paper, we use the above models framework to build a new regression model, called the twin proximal least squares support vector regression model based on heteroscedastic Gaussian noise (TPLSSVR-HGN). The least square method is introduced and the regularization terms b 1 2 and b 2 2 are added respectively. It transforms an inequality constraint problem into two simpler equality constraint problems, which not only improves the training speed and generalization ability, but also effectively improves the forecasting accuracy. In order to solve the parameter selection problem of model TPLSSVR-HGN, the particle swarm optimization algorithm with fast convergence speed and good robustness is selected to optimize its parameters. In order to verify the forecasting performance of TPLSSVR-HGN, it is compared with the classical regression models on the artificial data set, UCI data set and wind-speed data set. The experimental results show that TPLSSVR-HGN has better forecasting effect than the classical regression models.

High-resolution near infrared observations with GRAVITY instrument have revealed rapid orbital motions of a hot spot around Sgr A*, the supermassive black hole in our Galactic center, during its three bright flares. The projected distances of the spot to the black hole are measured and seems to increase with time. The values of distance, combined with the measured orbiting time, imply that the spot is rotating with a super-Keplerian velocity. These results are hard to understand if the spot stay within the accretion flow thus provide strong constraints on theoretical models for flares. Previously we have proposed a "ME" model for the flares by analogy with the coronal mass ejection model in solar physics. In that model, magnetic reconnection occurred at the surface of the accretion flow results in the formation of flux ropes, which are then ejected out. Energetic electrons accelerated in the current sheet flow into the flux rope region and their radiation is responsible for the flares. In this paper, we apply the model to the interpretation of the GRAVITY results by calculating the dynamics of the ejected flux rope, the evolution of the magnetic field and the energy distribution of accelerated electrons, and the radiation of the system. We find that the model can well explain the observed light curve of the flares, the time-dependent distance and the super-Keplerian motion of the hot spot. It also explains why the light curve of some flares have double peaks., 15 pages, 13 figures, accepted by MNRAS

A benzothiadiazole-based chromophore using the molecular design strategy of engineering multipolar charge distributions was synthesized and obtained a large nonlinear response.

By modifying the bridge group type and the anchor group configuration, conductance was considerably altered as a consequence of the addition of an efficient spatial transport channel.

Through a case study of Kunshan, China, this paper shows how a local state utilised place-based leadership to enhance regional economic resilience under the COVID-19 pandemic crisis. It unpacks how Kunshan effectively mitigated early economic disturbances induced by the COVID-19 pandemic, by two ways of leadership actions, namely, enacting jurisdictional power (that is formal leadership), and mobilising wide official and interpersonal networks (that is network leadership). Four specific local-state-led adaptive resilience processes or strategies are identified: stabilising labour supply, mitigating supply-chain disruptions, alleviating financial strains and reconfiguring market orientations. Through these proactive endeavours, the local state played an enabling role in aligning diverse stakeholders and resources across places, scales and sectors, thereby allaying economic shocks and enhancing regional economic resilience. This study contributes to the resilience literature by developing an agency-centric perspective to understanding regional economic resilience during the COVID-19 pandemic.

The Huangshan-Jingerquan belt in Northwest China is one of the most important orogen-hosted magmatic Ni-Cu sulfide metallogenic belts worldwide. The Huangshandong, Huangshan, and Tulaergen deposits are the three largest Ni-Cu deposits along the belt. The orebodies are situated inside mafic-ultramafic complexes. Sulfur isotope data and trace element composition of the sulfide ores and country rocks are used to evaluate the importance of crustal S addition for sulfide mineralization and speculate as to the source of the sulfur that triggered sulfide segregation. The S/Se ratios of >95% of the sulfide ores range from 2,398 to 85,222—higher than that of the mantle (2,850–4,350) but lower than the country rocks (S/Se = 3,889–160,769). The sulfide ores from the Huangshandong, Huangshan, and Tulaergen deposits have restricted δ34S values ranging from –0.86 to 1.33, 0.26 to 0.75, and –0.2 to 1.4‰, respectively. However, the country rocks of these mafic-ultramafic complexes have highly heterogeneous δ34S, ranging from –22.3 to 18.8, –22.3 to 2.12, and –1.4 to 5.3‰, respectively. Arsenic/bismuth and Sb/Bi ratios of the sulfide ores range from 0.22 to 7.59 and 0.02 to 2.88, respectively, which are lower than those of the country rocks (3.17–243 and 2.8–33) and mid-ocean ridge basalt (MORB) (5.09–127 and 0.51–9.25). The values of δ34S and S/Se as well as ratios of As/Bi and Sb/Bi of the sulfide ores indicate that the sulfide segregation and consequently the formation of the deposits were closely associated with the addition of crustal sulfur, whereas the sulfides in the country rocks have not been incorporated into the mineralization. Thus, it is proposed that assimilation of external crustal sulfur at depth might play a critical role in triggering sulfide immiscibility and the formation of the magmatic Ni-Cu deposits in the Huangshan-Jingerquan belt.

To describe the results of mesh exposure and prolapse recurrence of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) for sacrocolpopexy after more than 24 months of postoperative follow-up.A retrospective cohort study.A university hospital.Women with uterine prolapse who underwent vNOTES sacrocolpopexy with an ultralightweight polypropylene mesh between May 2018 and March 2020.vNOTES sacrocolpopexy.Of 57 women, 55 women (96.5%) were included in the final analysis. The mean follow-up duration was 35.5 ± 7.6 (24-46) months. The total incidence of mesh exposure was 3 of 55 (5.5%). The total incidence of prolapse recurrence was 3 of 55 (5.5%). The changes in the Pelvic Organ Prolapse Quantification System scores, including Aa, Ba, C, Ap, Bp, and total vaginal length values, showed significant improvement after surgery (p.05 for all).The study demonstrates that vNOTES sacrocolpopexy appears to be an effective option with low risks of mesh exposure and prolapse recurrence. Studies including more patients and longer follow-up periods should be performed before a clear conclusion can be reached.

Parkinson's disease (PD) is characterized as a neurodegenerative disease; however, the mechanisms regarding its pathogenesis have not been fully explored.To explore the role of circular RNA homeodomain interacting protein kinase 3 (circHIPK3) in the progression of PD.The circHIPK3 and microRNA-124 (miR-124) expression in human serum and cerebral fluid was detected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 92 PD patients and 95 controls. The circHIPK3 was overexpressed and/or silenced in cells to explore its molecular mechanisms and effects on neuroinflammation. The production of intracellular reactive oxygen species (ROS) was assessed using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Interleukin 6 (IL-6), IL-1β and tumor necrosis factor alpha (TNF-α) production in BV2 cells after the indicated treatment was measured using enzyme-linked immunosorbent assay (ELISA). The protein expression of microglia markers (cluster of differentiation molecule 11b (CD11b) and ionized calcium-binding adapter molecule 1 (Iba-1)), pyroptosis-related factors, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC), and caspase-1, signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) were examined using western blot analysis. Furthermore, the interaction between circHIPK3, miR-124 and STAT3 was predicted with bioinformatics and examined using fluorescence in situ hybridization (FISH), luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation (RIP).The expression of circHIPK3 in human serum and cerebral fluids was significantly higher than in controls, whereas miR-124 expression was drastically reduced. In addition, lipopolysaccharide (LPS)-treated BV2 cells exhibited higher expression of circHIPK3 and lower miR-124 expression. The SH-SY5Y cells exhibited a significantly impaired viability and elevated apoptotic rate, along with an upregulation of circHIPK3 and a downregulation of miR-124 expression after being treated with supernatants collected from LPS-treated BV2 cells. The upregulation of circHIPK3 increased IL-6, IL-1β and TNF-α secretion in BV2 cells. The protein expressions of microglia markers (CD11b and Iba-1), as well as pyroptosis-related factors, NLRP3, caspase-1, and ASC, were also increased following the expression of circHIPK3. All these effects were reversed by the addition of miR-124.The circHIPK3 enhances neuroinflammation by sponging miR-124 and regulating the miR-124-mediated STAT3/NALP3 pathway in PD.

DNA methylation (5-methylcytosine, 5mC) is the most prevalent epigenetic modification that is predominantly found in CG dinucleotides in mammalian genomes. In-depth investigation of the functions of 5mC heavily relies on the quantitative measurement of 5mC at single-base resolution in genomes. Here, we proposed a methyltransferase-directed labeling with APOBEC3A (A3A) deamination sequencing (MLAD-seq) method for the single-base resolution and quantitative detection of 5mC in DNA. In MLAD-seq, a mutant of DNA methyltransferase, M.MpeI-N374K, is utilized to selectively transfer a carboxymethyl group to the 5 position of cytosine in the CG dinucleotide to form 5-carboxymethylcytosine (5camC) using carboxy

Aim: Lower grade gliomas [LGGs; World Health Organization (WHO) grades 2 and 3], owing to the heterogeneity of their clinical behavior, present a therapeutic challenge to neurosurgeons. The aim of this study was to explore the N6-methyladenosine (m6A) modification landscape in the LGGs and to develop an m6A-related microRNA (miRNA) risk model to provide new perspectives for the treatment and prognostic assessment of LGGs. Methods: Messenger RNA (mRNA) and miRNA expression data of LGGs were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. An m6A-related miRNA risk model was constructed via least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analysis. Next, Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment analysis, immune infiltrate analysis, dynamic nomogram, and drug sensitivity prediction were used to evaluate this risk model. Results: Firstly, six m6A-related miRNAs with independent prognostic value were selected based on clinical information and used to construct a risk model. Subsequently, compared with low-risk group, LGGs in the high-risk group had a higher m6A writer and reader scores, but a lower eraser score. Moreover, LGGs in the high-risk group had a significantly worse clinical prognosis than those in the low-risk group. Simultaneously, this risk model outperformed other clinicopathological variables in the prognosis prediction of LGGs. Immune infiltrate analysis revealed that the proportion of M2 macrophages, regulatory T (Treg) cells, and the expression levels of exhausted immune response markers were significantly higher in the high-risk group than in the low-risk group. Finally, this study constructed an easy-to-use and free dynamic nomogram to help clinicians use this risk model to aid in diagnosis and prognosis assessment. Conclusions: This study developed a m6A-related risk model and uncovered two different m6A modification landscapes in LGGs. Moreover, this risk model may provide guidance and help in clinical prognosis assessment and immunotherapy response prediction for LGGs.

Sustainable design does not emphasize the safety of the ecosystem, but builds a systematic innovation process, taking into account customer needs, environmental benefits, social benefits, and corporate development. This article is based on the preparation of a modified carbon nanotube polyvinylidene fluoride composite film to analyze its application value in packaging design, aiming at analyzing the performance of the modified carbon nanotube and the polyvinylidene fluoride composite film during the preparation process, and applying its various characteristics to the process of packaging design optimization concept. The article is mainly divided into two parts: preparing modified carbon nanotubes and preparing polyvinylidene fluoride composite films. Among them, the photomechanical properties of carbon nanotubes, the relationship between the composition of the composite material and the dielectric properties, the dielectric response and relaxation behavior, the hydrophilicity of the composite membrane, and the membrane separation technology were discussed, and the carbon nanotubes were constructed. Incorporating carbon nanotubes into carbon fiber hybrid materials, and combining carbon nanotubes with polymer materials, works extremely well. The structure model is prepared, the molecular pore size, hydrophilicity, etc. are recorded, and surface modification, chemical modification, blending modification, and other methods are applied to analyze and evaluate the data. The experimental results show that in the application of modified carbon nanotubes and polyvinylidene fluoride composite films and packaging design, the interactive function of toughening modification increases 2.44 points; through enhancement modification, packaging design reduction increases by 2.5 points; and through the compatibilization modification, the functionality of the packaging design has increased by 1.88 points.

RNA molecules harbor diverse modifications that play important regulatory roles in a variety of biological processes. Over 150 modifications have been identified in RNA molecules. N6-methyladenosine (m6A) and 1-methyladenosine (m1A) are prevalent modifications occurring in various RNA species of mammals. Apart from the single methylation of adenosine (m6A and m1A), dual methylation modification occurring in the nucleobase of adenosine, such as N6,N6-dimethyladenosine (m6,6A), also has been reported to be present in RNA of mammals. Whether there are other forms of dual methylation modification occurring in the nucleobase of adenosine other than m6,6A remains elusive. Here, we reported the existence of a novel adenosine dual methylation modification, i.e. 1,N6-dimethyladenosine (m1,6A), in tRNAs of living organisms. We confirmed that m1,6A is located at position 58 of tRNAs and is prevalent in mammalian cells and tissues. The measured level of m1,6A ranged from 0.0049% to 0.047% in tRNAs. Furthermore, we demonstrated that TRMT6/61A could catalyze the formation of m1,6A in tRNAs and m1,6A could be demethylated by ALKBH3. Collectively, the discovery of m1,6A expands the diversity of RNA modifications and may elicit a new tRNA modification-mediated gene regulation pathway.