Proteomic Profiling of Messenger Ribonucleoproteins in Mouse Tissues Based on Formaldehyde Cross-Linking.

Messenger ribonucleoprotein particles (mRNPs) are vital for tissue-specific gene expression via mediating posttranscriptional regulations. However, proteomic profiling of proteins in mRNPs, i.e., mRNA-associated proteins (mRAPs), has been challenging at the tissue level. Herein, we report the development of formaldehyde cross-linking-based mRNA-associated protein profiling (FAXRAP), a chemical strategy that enables the identification of mRAPs in both cultured cells and intact mouse organs. Applying FAXRAP, tissue-specific mRAPs were systematically profiled in the mouse liver, kidney, heart, and brain. Furthermore, brain mRAPs in Parkinson's disease (PD) mouse model were investigated, which revealed a global decrease of mRNP assembly in the brain of mice with PD. We envision that FAXRAP will facilitate uncovering the posttranscriptional regulation networks in various biological systems.

Endoscopic spraying of smectite for preventing esophageal stricture after endoscopic submucosal dissection.

Esophageal stenosis after ESD has been recorded high for large-scale esophageal lesion. Risk factors for increasing the occurrence of stenosis includes long type lesions, lesions infiltrating into the muscularis mucosa and muscular layer injury. In this case, postoperative stricture of the patient was highly likely occurred. Smectite is a mucosal protective agent that can resist external stimuli, promote wound healing, and reduce inflammatory factors. Therefore, it can effectively prevent the formation of scars on wounds. This study was carried out in humans for the first time and was successful. In conclusion, endoscopic spraying of smectite may be effective and safe in preventing esophageal stenosis after ESD with large non-circumferential lesions.

Phenotypic variations induced emergence of orientation order and morphology in Bacillus subtilis biofilm growth.

During the Bacillus subtilis biofilm growth on the solid MSgg substrate, the biofilm exhibits highly ordered structures such as matrix-producing-cell chains and Van Gogh bundles due to bacterial orientation order. These structures make the biofilm have strong mobility and environmental adaptability, thus making bacteria easier to survive and thrive in biofilms comparing to planktonic bacteria. We tested the behaviors of different phenotypes as well as their impacts on bacterial clusters: motile cells arrange disorderly, the biofilm made up of motile cells tends to be circular and isotropic; matrix-producing cells form cellular chains that guide motile cells along the chain to form a locally nematic phase, the morphology of the biofilm made up of both motile cells and matrix-producing cells is rendered irregular. Combining the results of a coarse-grained and individual-based model, we can control the biofilm growth through regulating environmental friction, bacterial growth rate and adhesion between cells.

Facile Synthesis of Clickable Unnatural Sugars in the Unprotected and 1,6-Di-O-Acylated Forms for Metabolic Glycan Labeling.

Clickable unnatural sugars have been widely used in studying glycosylation in living systems via the metabolic glycan labelling (MGL) strategy. Partial protection of unnatural sugars by 1,6-di-O-acylation increases the labelling efficiency while avoiding the non-specific S-glyco-modification. Herein, we report the facile synthesis of a series of clickable unnatural sugars in both the unprotected and 1,6-di-O-acylated forms at the ten-gram scale. By evaluation of the labelling specificity, efficiency, and biocompatibility of various 1,6-di-O-acylated sugars for MGL in cell lines and living mice, we demonstrate that 1,6-di-O-propionylated unnatural sugars are optimal chemical reporters for glycan labelling. The synthetic routes developed in this work should facilitate the widespread use of MGL with no artificial S-glyco-modification for investigating the functional roles of glycans.

Analysis of biofilm expansion rate of Bacillus subtilis (MTC871) on agar substrates with different stiffness.

The surface morphology of mature biofilms is heterogeneous and can be divided into concentric rings wrinkles (I), labyrinthine networks wrinkles (II), radial ridges wrinkles (III), and branches wrinkles (IV), according to surface wrinkle structure and distribution characteristics. Due to the wrinkle structures, channels are formed between the biofilm and substrate and transport nutrients, water, metabolic products, etc. We find that expansion rate variations of biofilms growing on substrates with high and low agar concentrations (1.5, 2.0, 2.5 wt.%) are not in the same phase. In the first 3 days' growth, the interaction stress between biofilm and each agar substrate increases, which makes the biofilm expansion rate decreases before wrinkle pattern IV (branches) comes up. After 3 days, in the later growth stage after wrinkle pattern IV appears, the biofilm has larger expansion rate growing on 2.0 wt.% agar concentration, which has the larger wrinkle distance in wrinkle pattern IV reducing energy consumption. Our study shows that the stiff substrate does not always inhibit the biofilm expansion, although it does in the earlier stage; after that, mature biofilms acquire larger expansion rate by adjusting the growth mode through the wrinkle evolution even in nutrient extremely depletion.

The formation mechanism of Bacillus subtilis biofilm surface morphology under competitive environment.

Material properties and growth environments affect the surface morphology of biofilms. Taken the biofilm growing in competitive environments as the object, which is compared with the single biofilm, we find that the competitive environment has an impact on the biofilm thickness and wrinkle patterns. Through diffusion-limited growth theoretical model analysis, it shows that the competitive environment is caused by cells competing for nutrition, and the competitive environment reacts on biofilms, which affect the phenotypic differentiation, causing changes in the stiffness of the biofilm. Using the theoretical and finite element simulation, we compare these results of bi-layer and tri-layer film-substrate models with experimental observations, and find that tri-layer film-substrate model is in line with the reality, which means that the layer between the biofilm and substrate plays an import role for wrinkle formation. Based on the above analysis, we further study effects of biofilm stiffness and interlayer thickness on wrinkles under competitive environment.

Endoscopic resection of a descending duodenal polyp with the string-clip traction.

There is few studies about modified endoscopic treatment of duodenal lesions. The string-clip method is an effective option for large pedunculated duodenal polyp. On the one hand, it could increase the tension of the lesion and make endoscopic resection easy. What is more, with the help of clip and dental floss, we do not have to worry about specimen losing. We could deal with the wound first and then retrieve the resected specimen, resulting in an increased safety and efficiency of the endoscopic treatment.

Matrix Producing Cells Induce the Morphological Difference in the Bacillus subtilis Biofilm.

There is a 'coffee ring' in the Bacillus subtilis biofilm center, and the colony biofilm morphologies are distinct inside and outside the 'coffee ring'. In this paper, we study this morphological difference and explain the reasons of the 'coffee ring' formation and further the causes to the morphological variation. We developed a quantitative method to characterize the surface morphology, the outer area is thicker than the inner area of the 'coffee ring', and the thickness amplitude in outer area is larger than inner area of the 'coffee ring'. We adopt a logistic growth model to obtain how the environmental resistance influence the colony biofilm thickness. Dead cells provide gaps for stress release and make folds formation in colony biofilm. we developed a technique for optical imaging and matching cells with the BRISK algorithm to capture the distribution and movement of motile cells and matrix producing cells in the colony biofilm. Matrix producing cells are mainly distribute in the outside of the 'coffee ring', and the extracellular matrix (ECM) prevents the motile cells moving outward from center. Motile cells mainly locate inside the ring, a small amount of dead motile cells outside the 'coffee ring' give rise to radial folds formation. There are no ECM blocking cell movements inside the ring, which result in uniform folds formation. The distribution of ECM and different phenotypes lead to the formation of the 'coffee ring', which is verified by using eps and flagellar mutants.

Click-iG: Simultaneous Enrichment and Profiling of Intact N-linked, O-GalNAc, and O-GlcNAcylated Glycopeptides.

Proteins are ubiquitously modified with glycans of varied chemical structures through distinct glycosidic linkages, making the landscape of protein glycosylation challenging to map. Profiling of intact glycopeptides with mass spectrometry (MS) has recently emerged as a powerful tool for revealing matched information of the glycosylation sites and attached glycans (i.e., intact glycosites), but is largely limited to individual glycosylation types. Herein, we describe Click-iG, which integrates metabolic labeling of glycans with clickable unnatural sugars, an optimized MS method, and a tailored version of pGlyco3 software to enable simultaneous enrichment and profiling of three types of intact glycopeptides: N-linked, mucin-type O-linked, and O-GlcNAcylated glycopeptides. We demonstrate the utility of Click-iG by the identification of thousands of intact glycosites in cell lines and living mice. From the mouse lung, heart, and spleen, a total of 2053 intact N-glycosites, 262 intact O-GalNAc glycosites, and 1947 O-GlcNAcylation sites were identified. Click-iG-enabled comprehensive coverage of the protein glycosylation landscape lays the foundation for interrogating crosstalk between different glycosylation pathways.

Prediction of metasurface spectral response based on a deep neural network.

The two-dimensional optical metasurface can realize the free regulation of light waves through the free design of structure, which is highly appreciated by researchers. As there are high requirements for computer hardware, long time for simulation calculations, and data waste in the process of using the time-domain finite-difference method to solve the optical properties of the metasurface, the deep neural network (DNN) is proposed to predict the spectral response of an optical metasurface. The structural parameters of the metasurface are taken as inputs and the metasurface transmission spectrum is used as the output. To achieve better prediction results, different gradient descent algorithms were selected and the parameters of the DNN model were optimized. After 5 × 104 times of epoch training, the loss function mean squared error (MSE) reaches 2.665 × 10-3, the sum error of 98% test data is less than 3.23, and the relative error is less than 2%. The results show that the DNN model has an excellent prediction effect. Compared with the traditional simulation method, the efficiency of this model is improved by 104 times, which can improve the efficiency of optical micro-nano structure design.

Peroxynitrite-Promoted Persulfide Prodrugs with Protective Potential against Paracetamol Poisoning.

The newly emerging persulfide prodrugs provide additional options for the profound study of persulfide, a fascinating molecule expected to intervene in biological functions and even diseases. Peroxynitrite is often the culprit in pathological processes characterized by oxidative stress, while the persulfide prodrug responsive to it is still pending. To enrich the family of redox-activated prodrugs, we designed prodrugs with a 2-oxo-2-phenylacetamide trigger, which achieved the release of persulfide via 1, 6-N, S-relay. The degradation of prodrugs and the formation of persulfides were confirmed to be peroxynitrite-responsible by the qualitative and quantitative studies based on LC-MS/MS methods and a spectrophotometry-based tag-switch strategy. Furthermore, these prodrugs showed potent peroxynitrite scavenging activity, cellular therapeutic potential against paracetamol poisoning in HepG2 and oxidative stress in H9c2, as well as desirable in vitro metabolic properties.

Appropriate duration of endoscopic dilation for postoperative benign esophageal strictures.

BACKGROUND: Benign esophageal strictures are a frequent complication after esophageal surgery or extensive endoscopic submucosal dissection. Endoscopic dilation is the preferred treatment in clinical practice. However, the allocation of time for each dilation is unclear. The aim of this study was to evaluate the appropriate duration of endoscopic dilation for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection. METHODS: Patients with benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection between July 2010 and July 2018 were retrospectively included in this study. According to the dilation time (1, 3, 5 min), patients were divided into three groups. The clinical effects and adverse events were compared among the three groups. RESULTS: Altogether, 57 patients, including 21 in the 1-min group, 18 in the 3-min group and 18 in the 5-min group, were included. All patients underwent endoscopic treatment successfully. The stricture recurrence rate was 76.19% in the 1-min group, 55.56% in the 3-min group and 61.11% in the 5-min group. The median overall dysphagia-free period was 2.60 (range, 0.80-12.00) months in the 1-min group, 6.60 (range, 1.80-12.00) months in the 3-min group and 6.25 (range, 2.40-12.00) months in the 5-min group (P < 0.05). For patients who developed stricture recurrence, the mean dysphagia-free periods were 2.26  ±  1.27 months, 4.00  ±  1.76 months and 4.23  ±  1.63 months, respectively (P < 0.05). The dysphagia-free periods were comparable between the 3- and 5-min groups and were longer than those in the 1-min group. Muscle layer damage occurred in two patients (11.11%) in the 5-min group and in no patients in the other two groups. CONCLUSION: Three minutes was considered a safe and effective dilation duration for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.

Clinical outcomes of endoscopic ultrasound-guided gastroenterostomy for gastric outlet obstruction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) has been used for gastric outlet obstruction (GOO) with promising clinical outcomes. Therefore, we aimed to determine the clinical outcomes of EUS-GE for GOO. MATERIAL AND METHODS: We used the keyword 'EUS-guided gastroenterostomy' to search in Pubmed, Web of science, Cochrane databases. Clinical outcomes of EUS-GE were evaluated in terms of technical success, clinical success and complications. RESULTS: Ten studies reported 297 patients managed with EUS-GE. Weighted pooled rates (WPR) for technical success, clinical success and complications of EUS-GE were 91% (95%CI 87%-94%), 88% (95%CI 83%-91%) and 6.8% (95%CI 4.1%-11.0%). The most common complications were abdominal pain, 6.7% (95%CI 2.5%-16.5%) and bleeding, 4.8% (95%CI 1.5%-13.9%). Two studies compared EUS-GE with surgical gastrojejunostomy (SGJ). Pooled risk ratio (RR) for technical success, clinical success and complications were 0.87 (0.78, 0.97), I2 = 0%; 0.92 (0.82, 1.04), I2 = 0%; 0.28 (0.11, 0.68), I2 = 0%. Three studies compared benign GOO with malignant GOO. RR for technical success and clinical success were 1.05 (0.82, 1.34), I2 = 0%; 0.98 (0.72, 1.33), I2 = 0%. CONCLUSIONS: Although EUS-GE and SGJ had similar clinical success rates, EUS-GE had a lower complication rate. EUS-GE is a safe, effective, and minimally invasive choice for patients with GOO.

Diethyl Azodicarboxylate-Promoted Oxidative [3 + 2] Cycloaddition for the Synthesis of Pyrrolo[2,1-a]isoquinolines.

A novel metal-free protocol for the effective and efficient construction of pyrrolo[2,1-a]isoquinolines via a diethyl azodicarboxylate (DEAD)-promoted oxidative [3 + 2] cycloaddition/aromatization tandem reaction is described. Instead of the reported two-component oxidation systems, DEAD, as the sole oxidant, could smoothly transfer the tertiary amines to azomethine ylides via oxidation-deprotonation tandem process. The reaction proceeded with a broad substrate scope, giving rise to products in moderate to good isolated yields.

Rapid on-site evaluation of touch imprints of biopsies improves the diagnostic yield of transbronchial biopsy for endoscopically nonvisible malignancy: a retrospective study.

OBJECTIVE: Rapid on-site evaluation has long been used for transbronchial needle aspiration or fine-needle aspiration to evaluate the adequacy of biopsy materials for the diagnosis of peripheral lung lesions. However, research on rapid on-site evaluation combined with transbronchial forceps biopsy in the diagnosis of lung carcinoma is rarely reported. Therefore, we aimed to investigate the value of rapid on-site evaluation during transbronchial forceps biopsy for endoscopically visible (tumor, infiltrative and necrotic) or nonvisible (compressive, nonspecific and normal) malignancy. METHODS: A retrospective analysis was performed between January 2015 and January 2019 in Taihe Hospital with 1216 lung cancer patients who underwent bronchoscopy procedures, and these patients were allocated into the rapid on-site evaluation group and non-rapid on-site evaluation group, depending on the timing of the procedure. According to endoscopic features, bronchoscopic appearance was described as endoscopically visible malignancy (tumor, infiltrative and necrotic) and endoscopically nonvisible malignancy (compressive, nonspecific and normal). The diagnostic yield was compared, and the concordance between the rapid on-site evaluation results and the final histology was analyzed. RESULTS: There was a statistically significant difference in the diagnostic yield between the rapid on-site evaluation and non-rapid on-site evaluation groups for endoscopically nonvisible malignancy (74.3% vs. 51.7%, P < 0.05). However, we found no significant improvement in terms of diagnostic yield for endoscopically visible malignancy (95.2% vs. 91.2%, P > 0.05). The rapid on-site evaluation results showed high-level concordance with histology in the diagnosis of squamous cell carcinoma, adenocarcinoma and small cell carcinoma, with kappa values of 0.749 (P < 0.05), 0.728 (P < 0.05) and 0.940 (P < 0.05), respectively. CONCLUSIONS: The findings demonstrated that the diagnostic yield of transbronchial biopsy for endoscopically nonvisible malignancy (compressive, nonspecific and normal) was significantly improved when rapid on-site evaluation was implemented. In addition, the rapid on-site evaluation results had high-level concordance with the final histological diagnosis.

Erratum: N-myc Downstream-Regulated Gene 2 (NDRG2) Promotes Bone Morphogenetic Protein 2 (BMP2)-Induced Osteoblastic Differentiation and Calcification by Janus Kinase 3 (JAK3)/Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway.

The authors have found that a picture in Figure 6C is needed to be corrected. Reference: SunYu Chen, JianKun Wang, Chao Cai, Xiaoyan Xie. N-myc Downstream-Regulated Gene 2 (NDRG2) Promotes Bone Morphogenetic Protein 2 (BMP2)-Induced Osteoblastic Differentiation and Calcification by Janus Kinase 3 (JAK3)/Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway. Med Sci Monit 2020; 26:e918541. DOI: 10.12659/MSM.918541.

Metasurface parameter optimization of Fano resonance based on a BP-PSO algorithm.

An all-dielectric metasurface is proposed, and the transmission spectrum is analyzed by numerical simulation. The Fano resonance line appears in the transmission spectrum. The mechanism of Fano resonance is analyzed based on multipole coupling theory. The mathematical model between structural parameters and spectral performance is established by the back propagation (BP) neural network. Then, the genetic algorithm, sparrow search algorithm, and particle swarm optimization (PSO) algorithms are used to find the structural parameters corresponding to the optimal performance. The result shows that the quality factor is increased by three times, reaching 3805, and the modulation depth is close to 100% after PSO optimization. Our study provides a new method for the design of metasurfaces and parameter optimization of optical micro-nano structures.

Efficacy of threading lasso fixation in repairing partial articular supraspinatus tendon avulsion lesions: a retrospective study.

BACKGROUND: The partial articular supraspinatus tendon avulsion (PASTA) lesion repair remains a topic of debate. We have performed in situ repair of PASTA lesions using a potentially viable threading lasso fixation technique. This retrospective case series aimed to evaluate the clinical outcomes of PASTA lesion repair using threading lasso fixation. To the best of our knowledge, this is the first study to review this technique and its outcomes in terms of pain and upper extremity function. METHODS: Twenty-five patients with PASTA lesions who were treated with threading lasso fixation were reviewed. All patients were followed up for at least 1 year. Preoperative and follow-up data were retrospectively collected and reviewed. Clinical outcomes were assessed to evaluate the efficacy of the surgery. RESULTS: There were no postoperative complications. The average follow-up period was 25.7 (22-27) months. At the last follow-up, all patients underwent follow-up magnetic resonance imaging; only two cases showed a partially healed tendon and no case converted to full-thickness tear. Furthermore, shoulder pain decreased and mobility was recovered, with statistically significant differences in all scoring measures. Specifically, the mean visual analog scale score decreased from 5.4 ± 1.2 before surgery to 1.1 ± 0.8 at the last follow-up (t = 14.908, P < 0.01), and the mean American Shoulder and Elbow Surgeons Shoulder Assessment Form score improved significantly from 51.6 ± 6.4 to 89.3 ± 5.2 (t = 22.859, P < 0.01). Additionally, the mean University of California Los Angeles score improved from 17.8 ± 3.5 preoperatively to 32.3 ± 1.4 (t = 19.233, P < 0.01). CONCLUSIONS: Arthroscopic repair using threading lasso fixation is a novel transtendinous technique for patients with partial articular supraspinatus tendon avulsion. Tendon integrity is preserved with this method, which may result in improved function. Overall, threading lasso fixation technique is an effective treatment.

Frequency comb with 100 GHz spacing generated by an asymmetric MQW passively mode-locked laser.

A L-band two-section AlGaInAs/InP asymmetric multiple quantum well (QW) passively mode-locked laser has been used to generate a frequency comb with a 100 GHz spacing at a central wavelength of 1610 nm. The comb contains 10 optical lines within a -3dB bandwidth of 8.05 nm and 34 optical lines within a -20dB bandwidth of 30 nm. The mode-locked pulse duration was 440 fs. To the best of our knowledge, this is the shortest pulse duration from any directly electrically pumped QW semiconductor mode-locked laser.

Autophagy promotion enhances the protective effect of Morroniside on human OA chondrocyte.

Morroniside plays a therapeutic role in knee osteoarthritis (OA) by protecting chondrocytes. PI3K/AKT signaling is involved in the regulation of chondrocytes by Morroniside. PI3K/AKT suppresses autophagy through downstream signaling. However, the regulation of chondrocyte autophagy by Morroniside and the significance of the above effect on protecting chondrocytes aren't clear. The results showed that Morroniside inhibited the autophagiy of human OA chondrocytes. Besides, both PI3K inhibitors and mTOR inhibitors significantly reversed the autophagy reduced by Morroniside, but had no effect on the protective effect of Morroniside on chondrocytes. However, the enhanced autophagy caused by overexpression of autophagic genes enhanced the protective effect of Morroniside on chondrocytes. In conclusion, Morroniside represses the autophagy of human OA chondrocyte, which is related to PI3K/mTOR pathway. Moreover, the upregulation of autophagy further promoted the role of Morroniside in treating chondrocytes. Our data present a potential clue for the therapeutic strategies of Morroniside in treating OA.