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Approximately 22 nucleotide-long non-coding small RNAs (ncRNAs) play crucial roles in physiological and pathological activities, including microRNAs (miRNAs). Long ncRNAs often stay in the cytoplasm, modulating post-transcriptional gene expression. Briefly, miRNA binds with the target mRNA and builds a miRNA-induced silencing complex to silence the transcripts or prevent their translation. Interestingly, data from recent animal and plant studies suggested that mature miRNAs are present in the nucleus, where they regulate transcriptionally whether genes are activated or silenced. This significantly broadens the functional range of miRNAs. Here, we reviewed and summarized studies on the functions of nuclear miRNAs to better understand the modulatory networks associated with nuclear miRNAs.

Additional file 3: Table S2. miR-125b-5p predicted targets from miRWalk.

Additional file 4: Table S1. Primers used in the present study.

Additional file 1: Figure S1. Cell distribution of BALF of in PBS or Der f1-treated mice; Figure S2. Full length blot for Figure 5D.

Additional file 2: Table S1. miR-125b-5p predicted targets from ENCORI.

Additional file 4: Fig. S2. The LINC01003/CAV1 axis regulates glioma in vitro and in vivo.A transwell assay was employed to determine the migration ability of U87MG cells. The migrating glioma cells were counted.Western blot was used to detect the expression levels of p-FAK in U87MG cells.An xenograft tumor model was generated by U87MG cells. The tumor volume and weight in nude mice were measured. Data represent the mean ± SD; * P < 0.05, ** P < 0.01, and ***P < 0.001.

Additional file 4: Table S3. lncRNA target miR-125b-5p.

Additional file 6: Fig. S3. The relationship between m6A enzymes with LINC01003.m6A enzymes may perturb the expression of LINC01003.The correlation between m6A enzymes with LINC01003 in glioma tissues from the GEPIA2 database.

Additional file 3: Fig. S1. CAV1 is upregulated in glioma tissues and cells.The expression of CAV1 in GBM, LGG, and normal brain tissues from the Gene Expression Profiling Interactive Analysis 2database.The expression of CAV1 in World Health Organizationgrade II–IV tumors from the Chinese Glioma Genome Atlasdatabase. Kaplan–Meier curves from theGEPIA2 orCGGA database determined the relevance between CAV1 expression and overall survival in each subtype or each grade of glioma patients.RT-qPCR was used to detect the expression level of CAV1 in U87MG and U251 cells with LINC01003 knockdown. * P < 0.05, ** P < 0.01, and ***P < 0.001.

ObjectiveTo evaluate the safety and efficacy of transvesical incision in the treatment of ejaculatory duct obstruction.MethodsThe clinical data of 26 male infertile patients with ejaculatory duct obstruction were retrospectively analysed at the First Affiliated Hospital of Zhengzhou University from June 2020 to August 2021. All patients were treated with seminal vesicle neck incision for ejaculatory duct obstruction. The general clinical characteristics, intraoperative conditions and postoperative effects on the patients were recorded, and the therapeutic effect was evaluated.ResultsThe ejaculatory duct was found through fenestration, and the seminal vesicle gland was smoothly entered in 25 patients (96.2%). Among them, 22 cases underwent bilateral endoscopy and three underwent unilateral endoscopy. Sperm appeared in 23 cases (88.5%) 3 months after surgery. The sperm concentration and motility postoperatively at 6 months were higher than that at 3 months postoperatively. No postoperative complications, such as epididymitis or retrograde ejaculation, occurred.ConclusionSearching for the ejaculatory duct via the neck of the prostatic utricle, assisted by a low-energy holmium laser, is a new method for the treatment of ejaculatory duct obstruction. Microscopic vision is clear using this approach and the postoperative complications are few, which has high value for clinical application.

Phosphorylation of the eukaryotic translation initiation factor 2 α-subunit (eIF2ɑ)，which subsequently upregulates activating transcription factor 4 (ATF4), is the core event in the integrated stress response (ISR) pathway. Previous studies indicate phosphorylation of eIF2ɑ in atrial tissue in response to atrial fibrillation (AF). This study investigated the role of ISR pathway in experimental AF by using a small-molecule ISR inhibitor (ISRIB). Accordingly, rats were subjected to coronary artery occlusion to induce myocardial infarction (MI), or sham operation, and received either trans-ISRIB (2 mg/kg/day, i.p.) or vehicle for seven days. Thereafter, animals were subjected to the AF inducibility test by transesophageal rapid burst pacing followed by procurement of left atrium (LA) for assessment of atrial fibrosis, inflammatory indices, autophagy-related proteins, ISR activation, ion channel, and connexin43 expression. Results showed a significant increase in the AF vulnerability and the activation of ISR in LA as evidenced by enhanced eIF2α phosphorylation. ISRIB treatment suppressed upregulation of ATF4, fibrosis as indexed by determination of α-smooth muscle actin and collagen levels, inflammatory macrophage infiltration (i.e., CD68 and iNOS/CD68-positive macrophage) and autophagy as determined by expression of LC3. Further, ISRIB treatment reversed the expression of relevant ion channel (i.e., Nav1.5, Cav1.2, and Kv4.3) and Cx43 remodeling. Collectively, the results suggest that the ISR is a key pathway in pathogenesis of AF, post-MI, and represents a novel target for treatment of AF. Significance Statement Activation of integrated stress response (ISR) pathway as evidenced by enhanced eIF2α phosphorylation in left atrium plays a key role in atrial fibrillation (AF). A small-molecule ISR inhibitor (ISRIB) reduces AF and atrial arrhythmogenic substrate. The mechanism of ISRIB may be mediated by suppressing ISR pathway-related cardiac fibrosis, inflammatory macrophage infiltration, autophagy, and restoring the expression of ion channel and Cx43. This study suggests a key dysfunctional role for ISR in pathogenesis of AF with implications for novel treatment.

During the mining process of coal mines, coal pillars are often formed in the goaf on three sides, and the stress behavior of coal seams has a significant impact on the safety of coal mines. The upper part of panel 3104 of Xinwang Coal Mine is the room-pillar goaf of the 2# coal seam, and the lower part is the goaf of the 7# coal seam. The same coal seam is adjacent to the goaf of panel 3102. Therefore, there are hidden dangers for safe mining in panel 3104 affected by the goaf on three sides. Through FLAC3D numerical simulation, on-site Pasat-M detection, microseismic monitoring, and support resistance measurement, the stress distribution law of surrounding rock in the working face is analyzed. The following conclusions are obtained. There are several high wave velocity stress concentration areas in the coal body of 3104 working face. During the mining of the working face, the mining influence 90m in front of the working face began to spread to the area of the left coal pillar, and the vertical stress at the left coal pillar began to increase. Stress concentration appears in 0–20m strata at the top of 3# coal seams. At the top of a 3# coal seam, the vertical stress concentration coefficient can reach 2 in the range of 4–12m. The influence range of 3104 working face mining advance can reach 200m. Under the influence of mining, a large number of microseismic events occurred at 160m above and 150m below 3# coal seam. This law has reference value for the mining strata behaviors of coal seams under similar conditions.

BackgroundCrohn’s disease (CD) is characterized by repetitive phases of remission and exacerbation, the quality of life of patients with CD is strongly influenced by disease activity, as patients in the active phase experience significantly worse symptoms. To investigate the underlying mechanism of how the course of CD is exacerbated based on the bi-directionality of the brain-gut axis (BGA), we conducted a multi-modality neuroimaging study that combined resting-state functional magnetic resonance imaging (rs-fMRI) with proton magnetic resonance spectroscopy (MRS) to detect abnormalities in the anterior cingulate cortex (ACC).Materials and MethodsClinical scales including Visual Analog Scale (VAS) and Hospital Anxiety and Depression Scale (HADS) were used to evaluate the degree of abdominal pain and mood state of participants. We made a comparison between CD patients in the active phase, the remission phase and healthy controls (HCs), not only employed the innovative wavelet-transform to analyze the amplitude of low frequency fluctuation (ALFF) but also compared the sensitivity of wavelet-transform and the traditional fast Fourier transform (FFT). Brain metabolites such as glutamate (Glu), myo-inositol (mIns) and gamma-aminobutyric acid (GABA) were also detected. Then correlation analysis was made to see whether changes in the ACC correlated with CD’s clinical symptoms.ResultsCD patients in the active phase showed higher VAS scores (p = 0.025), the scores of anxiety and depression were also higher (all p < 0.05). Wavelet-transform is slightly more sensitive in the current research. Patients in the active phase exhibited higher ALFF in the left ACC and the left superior frontal gyrus, medial (SFGmed). Patients in the active phase showed increased Glu levels in the ACC than patients in the remission phase or HCs (p = 0.039 and 0.034 respectively) and lower levels of mIns than HCs (p = 0.036). There was a positive correlation between mWavelet-ALFF values of the ACC and HADS-depression scores in CD patients (r = 0.462, p = 0.006). Besides, concentrations of Glu positively correlated with mWavelet-ALFF in the ACC in all participants (r = 0.367, p = 0.006).ConclusionAbnormal spontaneous activity and metabolic levels in the ACC were detected in CD patients in the active phase along with severer abdominal pain and worse mood state, these may contribute to the exacerbation of CD. Therefore, the ACC might be a potential neural alternative for managing the exacerbation of CD.

Additional file 1: Figure S1. The PR (precision-recall) curves of (a) Optimized XGBoost, (b) XGBoost, (c) support vector machine, (d) decision tree, (e) K-nearest neighbor, (f) logistic regression, and (g) random forest binary classifiers.

Additional file 10: Figure S8. The function of siVPS25-1 in glioma cells. (A) RTCA xCELLigence assay showed that transfection of siVPS25-1 suppressed the proliferation of U251 cells. (B) Transfection of siVPS25-1 suppressed the colony formation of U251 cells. (C) The VPS25-silenced U251 cells were arrested at the G0/G1 phase of the cell cycle. (D) The p-JAK1 and p-STAT1 was detected by western blot in NC and siVPS25-1 glioma cells. Data are mean �� SD from three independent experiments. *P

Additional file 9: Figure S7. The p-JAK2,3 and p-STAT2,3 was detected by western blot in NC and siVPS25 glioma cells.

Additional file 3: Figure S3. Expression of ESCRT subunits in glioma tissues based on tumor grade. (A) Expression of MVB12A, VPS25, CHMP2A, and IST1 in WHO grade II and WHO grade III/IV from GEO database. (B) Expression of VPS25 in WHO grade II and WHO grade III from TCGA database. (C) Expression of CHMP2A in WHO grade II and WHO grade III from TCGA database. (D) The overall survival of LGG or GBM patients with high and low levels of VPS25 was plotted from GEPIA2. (E) The correlation between VPS25 expression with IDH mutation status in glioma. *P

Additional file 2: Figure S2. mRNA expression of all ESCRT subunits in glioma from GEO database. *P

Additional file 11: Figure S9. The knockdown of METTL3, METTL14, and YTHDC1 in glioma cells. (A) RT-qPCR was performed to verify the knockdown efficiency of METTL3 in U87MG and U251 cells. (B) RT-qPCR was performed to verify the knockdown efficiency of METTL14 in U87MG and U251 cells. (C) RT-qPCR was performed to verify the knockdown efficiency of YTHDC1 in U87MG and U251 cells. (D) The total m6A modification level was detected in METTL3, METTL14, and YTHDC1-knockdown cells. (E) U251 glioma cells were used to evaluate proliferation after being transfected with siVPS25 and siMETTL3. (F) U251 glioma cells were used to evaluate proliferation after being transfected with siVPS25 and siMETTL14. *P

Additional file 6: Figure S6. VPS25 regulates glioma cell apoptosis. (A) TUNEL assays were performed on U87MG cells, statistical analysis is shown on the right. (B) TUNEL assays were performed on U251 cells, statistical analysis is shown on the right. Scale bars, 100 ��m. Data are mean �� SD from three independent experiments. * P

Additional file 5: Figure S5. The knockdown of VPS25 in glioma cells. (A) The relative VPS25 expression level in 2 glioma cell lines (U87MG and U251) was compared with those in 14 non tumor brain tissues. (B) The U87MG cells, which were transfected with NC and siVPS25-1, -2, -3 for 48 h, were harvested. Then RT-qPCR detected the expression of VPS25 in U87MG cells. (C) RT-qPCR detected the expression of VPS25 in U251 cells transfected with siRNA. Experiments were performed and presented as shown in B. ***P

Additional file 4: Figure S4. The protein expression of VPS25 in glioma. (A) The VPS25 was detected by western blot in GBM (n = 8) and normal brain tissues (n = 14). (B) Statistics of the VPS25 expression in A. N: normal brain tissues, G: GBM tissues, ***P

Additional file 6: Figure S1. Workflow plot of construction of ceRNA network.

Additional file 9: Figure S2. Expression of C1s and HSD3B7 in GBM based on patients. (A) Expression of C1s in GBM based on patient’s age. (B) Expression of C1s in GBM based on patient’s gender. (C) Expression of HSD3B7 in GBM based on patient’s age. (D) Expression of HSD3B7 in GBM based on patient’s gender.

Additional file 10: Figure S3. C1s and HSD3B7 are up-regulated in GBM tissues. Western blot detection of C1s and HSD3B7 expression in 12 cases of GBM tissue (T) and normal tissue (N).

Additional file 11: Figure S4. lncRNA-miRNA-mRNA ceRNA network verification. (A) Expression levels of C1s were detected by RT-PCR in miR-132-3p, miR-346, miR-584-3p, miR-874-3p-overexpressed U251 cells. (B) Expression levels of HSD3B7 were detected by RT-PCR in miR-132-3p, miR-346, miR-381-3p, miR-584-3p-overexpressed U251 cells. (C) Putative binding sequence between lncRNAs and miRNAs. (D) Relative luciferase activities of reporters containing lncRNA RP11-268F1.3, RP11-547C13.1, RP11-90M5.4. (E) RT-PCR analysis showed that C1s was downregulated in lncRNA RP11-268F1.3, RP11-547C13.1, RP11-90M5.4-silenced U251 cells. Data are mean ± SD from three independent experiments.* p

Additional file 1. Additional methods.

Output properties of Si based photovoltaic detectors were researched applying femtosecond pulses with different repetition rates. The output properties of these detectors with different load conditions were also researched. The linear response domain of PIN detector with external reverse bias voltage was found quite large for different femtosecond pulses repetition rates. The sensitivity of PN detector was found much higher when applying external reverse bias voltage with femtosecond repetition rate 76 MHz. The saturation effect of PN detector was attributed to the slow response speed of the photovoltaic detector.

Fluorescence properties of DCM solution and solid dyes were researched applying femtosecond pulses under linear and nonlinear excitation. The reabsorption was distinct in the solid dyes compared with that in solutions under similar conditions. Nonlinear fluorescence spectra of DCM and rhodamine 590 co-doped tunable laser dyes in ethanol were also researched. The energy transfer of rhodamine 590 to DCM was found to be neglectable in the nonlinear excitation spectra of the co-doped liquid dyes.

According to the results of the mechanical experiments and the CT images, the finite element model of the proximal femur was established. Using finite element method, postoperative biomechanical parameters can be comprehensive analyzed. The analysis can be grouped by the patient body weight, the angle of fracture line, the position and angle of cannulated screw, which may influence the result of the operation. In the 216 groups of the parameters, the relative displacement of the fracture position, the strain at the bottom of the screw hole, the max stress of the screw and the max strain of the proximal femur was used for planning and evaluation. After comparing and analyzing the displacement, strain and stress, the rational parameters of internal fixation for femoral neck fractures can be found. And optimal operation planning parameters can be found according to the theory of biomechanics.