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Aims: This study aimed to develop an AI algorithm for automated HER2 scoring in urothelial bladder cancer (UBCa) and assess the interobserver agreement using both manual and AI-assisted methods based on breast cancer criteria. Methods and Results: We utilized 330 slides from two institutions for initial AI development and selected 200 slides for the ring study, involving six pathologists (3 senior, 3 junior). Our AI algorithm achieved high accuracy in two independent tests, with accuracies of 0.94 and 0.92. In the ring study, the AI-assisted method improved both accuracy (0.66 vs 0.94) and consistency (kappa=0.48; 95 % CI, 0.443–0.526 vs kappa=0.87; 95 % CI, 0.852–0.885) compared to manual scoring, especially in HER2-low cases (F1-scores: 0.63 vs 0.92). Additionally, in 62.3 % of heterogeneous HER2-positive cases, the interpretation accuracy significantly improved (0.49 vs 0.93). Pathologists, particularly junior ones, experienced enhanced accuracy and consistency with AI assistance. Conclusions: This is the first study to provide a quantification algorithm for HER2 scoring in UBCa to assist pathologists in diagnosis. The ring study demonstrated that HER2 scoring based on breast cancer criteria can be effectively applied to UBCa. Furthermore, AI assistance significantly improves the accuracy and consistency of interpretations among pathologists with varying levels of experience, even in heterogeneous cases.

Abstract The welding workshop of metal structural parts is highly energy-consuming. To meet the national low-carbon green demand, this paper focus on the welding workshop scheduling problem in production process with considering the carbon footprints such as equipment energy consumption, welding material consumption and shielding gas consumption. Firstly, a bi-objective low-carbon welding scheduling mathematical model is established with minimizing makespan and carbon emission. Then, an improved Grey Wolf Optimizer (IGWO) with three strategies is designed to solve this multi-objective problem. The grey wolf multi-wandering strategy (first) is proposed to enhance the population diversity. The grey wolf coordinated hunting strategy (second) based on dynamic weights is introduced to improve the convergence of IGWO. A local optimization strategy(third) is designed to improve the post-optimal search performance by adjusting the machine assignment based on the critical path. A welding workshop green scheduling case is designed to verify the model and algorithm proposed in this paper. The minimum completion time and carbon emissions obtained by the IGWO algorithm are 842.14 and 3.85E + 05, respectively. This result is better than that obtained by NSGA-II and GWO.The results show that the model effectively reduce the carbon emissions of the workshop, and the algorithm can effectively solve the model.

Abstract This study aimed to investigate the structural properties of tobacco polysaccharide (TP) and its mechanism of modulating hyperlipidemia in high-fat diet-induced mice. The structural properties of TP were characterized by FT-IR, 1HNMR, SEM, AFM and thermogravimetric analysis. And the regulatory mechanism of TP on lipid metabolism was investigated in hyperlipidemia mice. These results showed that TP had a high composition of reducing monosaccharide and the glycosidic bond type was α-glycosidic bond. The intervention by TP resulted in a significant reduction of body weight and improvement in lipid accumulation. And the modulation mechanism by which TP ameliorated the abnormalities of lipid metabolism was associated with the expression levels of lipid metabolism-related genes and serum exosomes miRNA-128-3p, as well as the modulation of structure and abundance of the gut microbiota in mice. In addition, TP treatment significantly increased the content of short-chain fatty acids (SCFAs) in mice feces. The results of molecular docking and dual-luciferase assay exhibited a good interaction between propionic acid and PPAR-α, and it was hypothesized that the interaction might further ameliorate the hyperlipidemia. Therefore, TP can regulate the expression levels of lipid metabolism-related genes through miRNAs from serum exosomes and SCFAs from gut microbiota.

Abstract Background This study aims to analyze potential differences in clinicopathology, efficacy of neoadjuvant therapy (NAT), and clinical outcome among HER2-null, HER2-ultralow and HER2-low breast cancers. Methods Consecutive cases of HER2-negative breast cancer that received NAT were included. They were classified as HER2-null (no staining), HER2-ultralow (incomplete faint staining in ≤ 10% of tumour cells) and HER2-low (HER2-1 + or HER2-2+, in situ hybridisation negative). Subgroup analysis was performed based on the HER2 expression level. Results Out of 302 patients, 215 (71.19%) were HER2-low, 59 (19.54%) were HER2-ultralow, and 28 (9.27%) were HER2-null. In comparison to the HER2-ultralow group, the HER2-low group exhibited higher expression frequencies of ER (p

This study aimed to investigate the effects of fermented soybean meal (FSM) on milk production, blood parameters, and rumen fermentation and microbial community in dairy cows. In this study, 48 healthy Holstein cows (parity, 3.0 ± 0.6; days in milk, 86.0 ± 6.7) were used. Cows were randomly assigned into four groups (CON, T-200, T-400, and T-600) with 12 cows per group. Cows in CON were not supplemented with FSM. Cows in T-200, T-400, and T-600 were supplemented with 200, 400, and 600 g/head/day FSM, respectively. This study lasted 5 weeks (1-week adaptation and 4-week treatment). The results showed that FSM did not affect milk yield and milk components (p > 0.05). In the serum, FSM greatly increased prolactin (p 0.05). In the rumen, FSM did not affect pH, microbial crude protein, acetate, propionate, butyrate, valerate, total volatile fatty acids and the ratio of acetate:propionate (p > 0.05), only changed NH3-N, isobutyrate and isovalerate (p

In this paper, the effect of the Si content on microstructure evolution, mechanical properties, and fracture behavior of the Al-xSi/AZ91D bimetallic composites prepared by compound casting was investigated systematically. The obtained results showed that all the Al-xSi/AZ91D bimetallic composites had a metallurgical reaction layer (MRL), whose thickness increased with increasing Si content for the hypoeutectic Al-Si/AZ91D composites, while the hypereutectic Al-Si/AZ91D composites were opposite. The MRL included eutectic layer (E layer), intermetallic compound layer (IMC layer) and transition region layer (T layer). In the IMC layer, the hypereutectic Al-Si/AZ91D composites contained some Si solid solution and flocculent Mg2Si+Al-Mg IMCs phases not presented in the hypoeutectic Al-Si/AZ91D composites. Besides, increasing Si content, the thickness proportion of the T layer increased, forming an inconsistent preferred orientation of the MRL. The shear strengths of the Al-xSi/AZ91D bimetallic composites enhanced with increasing Si content, and the Al-15Si/AZ91D composite obtained a maximum shear strength of 58.6 MPa, which was 73.4% higher than the Al-6Si/AZ91D composite. The fractures of the Al-xSi/AZ91D bimetallic composites transformed from the T layer into the E layer with the increase of the Si content. The improvement of the shear strength of the Al-xSi/AZ91D bimetallic composites was attributed to the synergistic action of the Mg2Si particle reinforcement, the reduction of oxidizing inclusions and the ratio of Al-Mg IMCs as well as the orientation change of the MRL.

Abstract Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS‐based magnetic beads (Mag‐CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV‐HCC patients. Leveraging data‐independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV‐HCC from CHB, LC, and non‐HCC conditions. Collectively, our findings highlight the utility of Mag‐CS‐based sEV isolation for identifying early detection biomarkers in HBV‐HCC.

Introduction We aim to assess the association between smoking behavior and intracranial aneurysms (IAs) and the effect of smoking cessation medications on IAs at the genetic level. Methods Causal effects of four phenotypes: 1) age at initiation of regular smoking, 2) cigarettes smoked per day, 3) smoking cessation, and 4) smoking initiation on IAs, were analyzed using two-sample inverse-variance weighted Mendelian randomization analyses. The effects of genes interacting with the smoking cessation medications were analyzed using cis-expression quantitative trait loci genetic instruments on IAs using summary statistics-based Mendelian randomization analyses. Colocalization analyses were then used to test whether the genes shared causal variants with IAs. The role of confounding phenotypes as potential causative mechanisms of IAs at these gene loci was tested. Results Cigarettes smoked per day (OR=2.89; 95% CI:1.85–4.51) and smoking initiation on IAs (OR=4.64; 95% CI: 2.64–8.15) were significantly associated with IA risk. However, age at initiation of regular smoking (OR=0.54; 95% CI: 0.10–2.8) and smoking cessation (OR=6.80; 95% CI: 0.01–4812) had no overall effect on IAs. Of 88 genes that interacted with smoking cessation medications, two had a causal effect on IA risk. Genetic variants affecting HYKK levels showed strong evidence of colocalization with IA risk. Higher HYKK levels in the blood were associated with a lower IA risk. Gene target analyses revealed that cigarettes/ day could be a main mediator of HYKK’s effect on IA risk. Conclusions This study provides evidence supporting that smoking initiation on IAs and cigarettes/day may increase IA risk. Increased HYKK gene expression may reduce IA risk. This can be explained by the increased number of cigarettes consumed daily. HYKK could also reduce IA risk due to the positive effect of continuous abstinence and varenicline therapy on smoking cessation.

Abstract Background Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles in sEV biogenesis and their interaction with other cells. However, the study on vesicular glycoconjugates are far behind proteins and nucleic acids. Especially, the functions of sialic acids which are the terminal components of glycoconjugates, are poorly understood in sEV. Methods Sialic acid levels on sEV from plasma and bladder cancer cells were determined by ELISA and lectin blotting. Effects of sialylation on sEV uptake were determined by flow cytometry. Vesicular glycoproteins bearing sialic acids responsible for sEV uptake was identified by proteomics and density gradient centrifugation, and their site-specific sialylation functions were assayed by N-glycosylation site mutation. Effects of integrin β1 bearing sialic acids on the pro-metastatic function of sEV in vivo were explored using Balb/c nu/nu mice. Results (1) Increased sialic acid levels were observed in sEV from malignant bladder cancer cells. (2) Elimination of sialic acids on sEV impaired sEV uptake by recipient cells. (3) Vesicular integrin β1 bearing sialic acids was identified to play a key role in sEV uptake. (4) Desialylation of the hybrid domain of vesicular integrin β1 inhibited its binding to matrix fibronectin, and reduced sEV entry into recipient cells. (5) Sialylation on integrin β1 affected pro-metastatic function of sEV in Balb/c nu/nu mice. Conclusions Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells. Graphical Abstract

Abstract Background Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker. Methods An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC. Results Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis. Conclusions The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.

Goupi plaster, a representative preparation of black plaster, has demonstrated promising effects in treating knee osteoarthritis. However, high temperature used in traditional frying extraction may cause decomposition of its effective components, thus limiting the efficacy. This study aimed to explore the scientific nature of the traditional preparation technology of Goupi plaster, and to compare the effects of different extraction methods on the types of chemical components and the content of index components. The UPLC-Q-Exactive-MS and UPLC-MS/MS technologies which have high efficiency, sensitivity and accuracy, were used to qualitatively and quantitatively analyze the chemical components of Goupi plaster under different preparation processes. The results show that the extraction solvent approach is different from the traditional frying extraction method, and has a positive effect. However, the mechanism of action of Goupi plaster is complex and its pharmacological effects are diverse. Future studies should explore whether it necessary to change the frying extraction method. This experiment provides a theoretical basis that will guide further scientific discussion and research into the frying extraction of Goupi plaster.

Abstract The functions of macrophages are governed by distinct polarization phenotypes, which can be categorized as either anti-tumor/M1 type or pro-tumor/M2 type. Glycosylation is known to play a crucial role in various cellular processes, but its influence on macrophage polarization is not well-studied. In this study, we observed a significant decrease in bisecting GlcNAc during M0-M1 polarization, and impaired bisecting GlcNAc was found to drive M0-M1 polarization. Using a glycoproteomics strategy, we identified Lgals3bp as a specific glycoprotein carrying bisecting GlcNAc. A high level of bisecting GlcNAc modification facilitated the degradation of Lgals3bp, while a low level of bisecting GlcNAc stabilized Lgals3bp. Elevated levels of Lgals3bp promoted M1 polarization through the activation of the NF-кB pathway. Conversely, the activated NF-кB pathway significantly repressed the transcription of MGAT3, leading to reduced levels of bisecting GlcNAc modification on Lgals3bp. Overall, our study highlights the impact of glycosylation on macrophage polarization and suggests the potential of engineered macrophages via glycosylated modification. Video Abstract

Hysterothylacium aduncum is one of six pathogens responsible for human anisakiasis. Infection with H. aduncum can cause acute abdominal symptoms and allergic reactions and is prone to misdiagnosis in clinical practice. This study aims to enhance the efficiency and accuracy of detecting H. aduncum in food ingredients. We targeted the internal transcribed spacer 1 (ITS 1) regions of Anisakis to develop a visual screening method for detecting H. aduncum using recombinase polymerase amplification (RPA) combined with the CRISPR/Cas12a system. By comparing the ITS 1 region sequences of eight nematode species, we designed specific primers and CRISPR RNA (crRNA). The specificity of RPA primers was screened and evaluated, and the CRISPR system was optimized. We assessed its specificity and sensitivity and performed testing on commercial samples. The results indicated that the alternative primer ADU 1 was the most effective. The final optimized concentrations were 250 nM for Cas12a, 500 nM for crRNA, and 500 nM for ssDNA. The complete test procedure was achievable within 45 min at 37 °C, with a limit of detection (LOD) of 1.27 pg/μL. The amplified product could be directly observed using a fluorescence microscope or ultraviolet lamp. Detection results for 15 Anisakis samples were entirely consistent with those obtained via Sanger sequencing, demonstrating the higher efficacy of this method for detecting and identifying H. aduncum. This visual detection method, characterized by simple operation, visual results, high sensitivity, and specificity, meets the requirements for food safety testing and enhances monitoring efficiency.

The extremely-low-frequency (ELF) magnetic fields of submarines serve as key characteristics for target detection, with their formation mechanisms being complex and diverse. Effectively manipulating a submarine to reduce its magnetic signature is crucial for enhancing its magnetic stealth capabilities. However, current research on the impact of various causative factors is insufficient. This study proposes a contribution rate assessment method based on the Analytic Hierarchy Process (AHP) model, aiming to provide a theoretical basis for effective manipulation. Initially, a thorough analysis of the threat causes of a submarine’s ELF magnetic fields is conducted, and a corresponding hierarchical threat structure model is established. Subsequently, magnetic field signal characteristics generated by different causes are obtained through simulation, and threat matrices and characteristic matrices are constructed. Finally, the contribution rates of different causative magnetic fields to the total magnetic field are calculated, and the simulation results validate the effectiveness of the method. At the stern detection line, the contribution rate of the wake magnetic field is the highest, reaching 0.7649. Along the radial detection line, the contribution rate of the shaft frequency magnetic field is the highest and gradually decays, eventually falling below the wake magnetic field at 150 m and remaining at an approximately 0.5 contribution rate. This study calculates the contribution rates under different operational conditions and detection scenarios, laying a technical foundation for research on the comprehensive active control strategies of submarine ELF magnetic fields in different scenarios.

Additive/subtractive hybrid manufacturing (ASHM) based on laser powder bed fusion (LPBF) enables to achieve high precision and good surface quality of complex structures such as small holes with overhanging features. However, the rapid heating and cooling rates during the ASHM results in sinkage at the alternating interface of additive manufacturing and subtractive milling, which degrades the surface quality of the components. This study employs shielding height at the alternating interface to solve this problem and improve the surface quality. The effect of internal diameters and shielding heights on the surface quality were studied experimentally for overhanging holes fabricated by ASHM of Ti6Al4V. The results show that the Ti6Al4V samples prepared by LPBF possessed high density and uniformly distributed microstructure. For overhanging holes without shielding height, the largest depth value of sinkage and surface roughness were obtained, indicating a worse surface quality; when the shielding height was increased to 0.5 mm, the smallest sinkage value and surface roughness were obtained, indicating a better surface quality. With the same shielding height, the overhanging holes with different diameters had a similar surface roughness. This study reveals that an appropriate shielding height can improve the surface quality, which provides guidance to the improvement of the surface quality for complex structures in ASHM.

ObjectiveIn order to solve the problem that noise detection inside a cabin is difficult due to the complexity and narrow space, a local space planning method of a manipulator based on the goal-oriented rapidly-exploring random tree (RRT) algorithm is proposed. MethodA six-degrees-of-freedom (6-DOF) manipulator is used as the carrier, and a fixture is installed at the end of the manipulator. The four fixed points inside the cabin are used as the reference points to study the mechanical arm in the local space. The trajectory planning is traversed and the reference point-1 is taken as an example to measure the noise of its 6 measurement surfaces and 147 measurement points. The noise signal and the position and attitude information of the space to be measured are matched and analyzed, and the environmental noise of the current measurement point is fed back to form a sound pressure cloud map. ResultsThe experimental results show that the robotic arm can realize trajectory planning and noise measurement for all measurement points corresponding to the four reference points without collision. ConclusionThe proposed method has practical value in being able to realize intelligent planning and internal noise detection in narrow cabin areas.

Abstract Background Microvascular decompression (MVD) is already the preferred surgical treatment for medically refractory neurovascular compression syndromes (NVC) such as hemifacial spasm (HFS), trigeminal neuralgia (TN), and glossopharyngeal neuralgia (GPN). Endoscopy has significantly advanced surgery and provides enhanced visualization of MVD. The aim of this study is to analyze the efficacy and safety of fully endoscopic microvascular decompression (E-MVD) for the treatment of HFS, TN, and GPN, as well as to present our initial experience. Materials and methods This retrospective case series investigated fully E-MVD performed in 248 patients (123 patients with HFS, 115 patients with TN, and 10 patients with GPN ) from December 2008 to October 2021 at a single institution. The operation duration, clinical outcomes, responsible vessels, intra- and postoperative complications, and recurrences were recorded. Preoperative and immediate postoperative magnetic resonance imaging (MRI) and computerized tomography (CT) were performed for imageological evaluation. The Shorr grading and Barrow Neurological Institute (BNI) pain score were used to evaluate clinical outcomes. The efficacy, safety, and risk factors related to the recurrence of the operation were retrospectively analysed, and the surgical techniques of fully E-MVD were summarised. Results A total of 248 patients (103 males) met the inclusion criteria and underwent fully E-MVD were retrospectively studied. The effective rate of 123 patients with HFS was 99.1%, of which 113 cases were completely relieved and 9 cases were significantly relieved. The effective rate of 115 patients with TN was 98.9%, of which 105 cases had completely pain relieved after surgery, 5 cases had significant pain relieved, 4 cases had partial pain relieved but still needed to be controlled by medication. The effective rate of 10 patients with GPN was 100%, 10 cases of GPN were completely relieved after surgery. As for complications, temporary facial numbness occurred in 4 cases, temporary hearing loss in 5 cases, dizziness with frequent nausea and vomiting in 8 cases, headache in 12 cases, and no cerebral hemorrhage, intracranial infection, and other complications occurred. Follow-up ranged from 3 to 42 months, with a mean of 18.6 ± 3.3 months. There were 4 cases of recurrence of HFS and 11 cases of recurrence of TN. The other effective patients had no recurrence or worsening of postoperative symptoms. The cerebellopontine angle (CPA) area ratio (healthy/affected side), the length of disease duration, and the type of responsible vessels are the risk factors related to the recurrence of HFS, TN, and GPN treated by fully E-MVD. Conclusions In this retrospective study, our results suggest that the fully E-MVD for the treatment of NVC such as HFS, TN, and GPN, is a safe and effective surgical method. Fully E-MVD for the treatment of NVC has advantages and techniques not available with microscopic MVD, which may reduce the incidence of surgical complications while improving the curative effect and reducing the recurrence rate.

Mg/Al bimetal combines the advantages of both aluminum and magnesium and has broad application prospects in automotive, aerospace, weapons, digital products and so on. The compound casting has the characteristics of low cost, easy to achieve metallurgical combination and suitable for the preparation of complex bimetallic parts. However, bimetallic joint strength is low due to differences of physical properties between Al and Mg, oxide film on metallic surface and interfacial Al-Mg IMCs, which is closely related to the interfacial microstructure and properties. Therefore, how to control the interface of the bimetal to achieve performance enhancement is the focus and difficulty in this field. At present, there are mainly the following strengthening methods. First, the “zincate galvanizing” and “electrolytic polishing+anodic oxidation” technology were exert on the surface of Al alloy to remove and break the oxide film, which improved the wettability between Al and Mg. Second, the undesirable Al-Mg IMCs were reduce or elimination by adding the interlayers (Zn, Ni and Ni-Cu). Thirdly, the evolution process of interfacial microstructure was changed and fine strengthening phases were formed by adding Si element to Al alloy or rare earth element to Mg alloy. Fourthly, mechanical vibration and ultrasonic vibration were applied in the process of the filling and solidification to refine and homogenize the interfacial structure. Finally, some other methods, including secondary rolling, thermal modification, heat treatment and constructing exterior 3D morphology, also can be used to regulate the interfacial microstructure and compositions. The above strengthening methods can be used alone or in combination to achieve bimetallic strengthening. Finally, the future development direction of the Mg/Al bimetal is prospected, which provides some new ideas for the development and application of the Mg/Al bimetal.

Abstract Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34+ cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse. Video Abstract

To improve the microstructure of compound casting Al/Mg bimetallic interface and optimize the bonding performance, the vibration assisted treatment and the Ni interlayer coating treatment were combined. After the composite treatment, the thickness of the Al/Mg bimetallic interface decreased significantly, only 8.13% of the original interface thickness. The original large amount of brittle and hard Al–Mg intermetallic compounds (IMCs) no longer existed, and were replaced by the (Mg–Ni) layer dominated by Mg3Ni2Al, the Al3Ni layer and the Ni solid solution layer. The shear crushing effect and the convective stirring effect of the vibration assisted treatment provided more stable and good metallurgical bonding for the Al/Mg bimetallic interface after introducing Ni interlayer. On this basis, combined with the second phase strengthening effect of the newly precipitating Mg3Ni2Al, the bonding strength of the Al/Mg bimetallic interface significantly improved, from 35.47 MPa to 56.12 MPa, with an increase of 58.22%.

Anisakiasis is a food-borne parasitic disease mainly caused by the third stage of Anisakis simplex (s. s.) and Anisakis pegreffii. Traditional methods for detecting of Anisakis involve morphology identification such as visual inspection, enzyme digestion, and molecular methods based on PCR, but they have certain limitations. In this study, the internal transcribed spacer 1 (ITS 1) regions of Anisakis were targeted to develop a visual screening method for detecting A. simplex (s. s.) and A. pegreffii in fish meat based on recombinase polymerase amplification (RPA) combined with lateral flow dipstick (LFD). Specific primers and probes were designed and optimized for temperature, reaction time, and detection threshold. LFD produced clear visual results that were easily identifiable after a consistent incubation of 10–20 min at 37 °C. The whole process of DNA amplification by RPA and readout by LFD did not exceed 30 min. In addition, the detection limit is up to 9.5 × 10−4 ng/μL, and the detection of the artificially contaminated samples showed that the developed assay can effectively and specifically detect A. simplex (s. s.) and A. pegreffii, which fully meet the market's requirements for fish food safety supervision.

Hirudo nipponia is an important medicinal animal in China. Its salivary gland secretions contain a variety of protein bioactive substances. Investigations of its salivary glands are of great significance in the study of the medicinal value and mechanism of leech secretions. Illumina RNA-Seq technology was used to perform transcriptome sequencing of salivary gland tissue of H. nipponia under starvation (D30) and fed (D0) states. A total of 2,650 differentially expressed genes (DEGs) were screened. Using the label-free protein quantification technique and bioinformatics analysis, the expression of differentially expressed proteins (DEPs) in the salivary gland tissue of H. nipponia was compared. A total of 2,021 proteins were identified, among which 181 proteins were differentially expressed between the starvation and fed states, with 72 significantly upregulated and 109 significantly downregulated. The salivary glands of H. nipponia synthesized protein-based active substances after 30 days of starvation and adapted to the starvation environment by weakening respiratory activity and reducing metabolic activity to reduce energy expenditure. Energy was produced by glycolysis and the tricarboxylic acid cycle for the synthesis of substances such as antibiotics. This study combined transcriptome and proteome sequencing data to provide a data reference for an in-depth study of the regulatory mechanism of salivary gland secretions of H. nipponia under starvation stress by analyzing DEGs and DEPs.

Bone marrow-derived mesenchymal stem cells (BMMSCs) derived from myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients often show a shift in the balance between osteoblastogenesis and adipogenesis. It was suggested that BMMSCs can potentially undergo reprogramming or educational processes. However, the results of reprogrammed differentiation have been inconclusive. In this study, clinical samples, co-culture models and mouse models were employed to explore the association of MDS/AML clonal cells and BMMSCs differentiation. We found that clonal MDS/AML cells promoted adipogenic differentiation and inhibited osteogenic differentiation of BMMSCs, which in turn promoted MDS expansion. Mass spectrometry and cytokine array were used to identify the molecules to drive the BMMSCs differentiation in MDS/AML. Mechanistically, highly expressed transcription factor TWIST1 in clonal MDS/AML cells induces MDS/AML cells to secrete more IFN-γ, which can induce oxidative stress through STAT1-dependent manner, ultimately causing enhanced adipogenic differentiation and inhibited osteogenic differentiation in BMMSCs. Overall, our findings suggest that targeting the driving oncogenes in malignant clonal cells, such as TWIST1, may offer new therapeutic strategies by remodeling the surrounding bone marrow microenvironment in the treatment of MDS/AML and other hematopoietic malignancies.

Abstract Background The tumour–stroma ratio (TSR) is identified as a promising prognostic parameter for breast cancer, but the cutoff TSR value is mostly assessed by visual assessment, which lacks objective measurement. The aims of this study were to optimize the cutoff TSR value, and evaluate its prognosis value in patients with breast cancer both as continuous and categorical variables. Methods Major clinicopathological and follow-up data were collected for a series of patients with breast cancer. Tissue microarray images stained with cytokeratin immunohistochemistry were evaluated by automated quantitative image analysis algorithms to assess TSR. The potential cutoff point for TSR was optimized using maximally selected rank statistics. The association between TSR and 5-year disease-free survival (5-DFS) was assessed by Cox regression analysis. Kaplan–Meier analysis and log-rank test were used to assess the significance in survival analysis. Results The optimal cut-off TSR value was 33.5%. Using this cut-off point, categorical variable analysis found that low TSR (i.e., high stroma, TSR ≤ 33.5%) predicts poor outcomes for 5-DFS (hazard ratio [HR] = 2.82, 95% confidence interval [CI] = 1.81–4.40, P = 0.000). When TSR was considered as a continuous parameter, results showed that increased stroma content was associated with worse 5-DFS (HR = 1.71, 95% CI = 1.34–2.18, P = 0.000). Similar results were also obtained in three molecular subtypes in continuous and categorical variable analyses. Moreover, in the Kaplan–Meier analysis, log-rank test showed that low TSR displayed a worse 5-DFS than high TSR (P = 0.000). Similar results were also obtained in patients with triple-negative breast cancer, human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and luminal–HER2-negative breast cancer. Conclusion TSR is an independent predictor for 5-DFS in breast cancer with worse survival outcomes in low TSR. The prognostic value of TSR was also observed in other three molecular subtypes.

Bisecting N-acetylglucosamine (GlcNAc), a GlcNAc linked to the core β-mannose residue via a β1,4 linkage, is a special type of N-glycosylation that has been reported to be involved in various biological processes, such as cell adhesion and fetal development. This N-glycan structure is abundant in human trophoblasts, which is postulated to be resistant to natural killer cell-mediated cytotoxicity, enabling a mother to nourish a fetus without rejection. In this study, we hypothesized that the human amniotic membrane, which serves as the last barrier for the fetus, may also express bisected-type glycans. To test this hypothesis, glycomic analysis of the human amniotic membrane was performed, and bisected N-glycans were detected. Furthermore, our proteomic data, which have been previously employed to explore human missing proteins, were analyzed and the presence of bisecting GlcNAc-modified peptides was confirmed. A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc, and 25 of these glycoproteins were reported to exhibit this type of modification for the first time. These results provide insights into the potential roles of bisecting GlcNAc modification in the human amniotic membrane, and can be beneficial to functional studies on glycoproteins with bisecting GlcNAc modifications and functional studies on immune suppression in human placenta.

In this work, a vibration was applied in the preparation of the Mg/Al bimetal by a novel compound casting in order to improve the mechanical properties of the Mg/Al bimetal, and the effect of the vibration on the interfacial microstructure and mechanical properties of the Mg/Al bimetal was investigated. The results indicated that the vibration had a significant effect on the interfacial microstructure and mechanical properties of the Mg/Al bimetal, but it did not change the phase compositions of the interface, which was composed of layer I (Al3Mg2+Mg2Si), layer II (Al12Mg17+Mg2Si) and layer III (Al12Mg17/δ-Mg). Without vibration, the Mg2Si phase with a needle-like morphology mainly aggregated in the layer II of the interface. After the application of the vibration, the SEM and EBSD analysis results showed that the Mg2Si and Al3Mg2 phases in the interface were obviously refined, and the distribution of the Mg2Si became more uniform, due to the strong forced convection of the molten metal resulting from the vibration. The TEM analysis indicated that the interface between the Al3Mg2 and Mg2Si phases was non-coherent, suggesting the Mg2Si particles cannot act as a heterogeneous nucleation base during the solidification process of the interface. Compared to the Mg/Al bimetal without vibration, the shear strength of the Mg/Al bimetal with vibration increased by about 50% from 31.7 MPa on average to 47.5 MPa, and the hardness of the layer I of the interface increased, and the hardness of the layer III decreased. The fracture surface transformed from a flat fracture morphology without vibration to an irregular zigzag fracture morphology.

High-performance polymer dielectrics are critical for high-tech fields such as electrical insulation and aerospace. Nevertheless, it is still challenging to achieve simultaneous improvements in both dielectric constant and breakdown strength in polymer dielectrics. In this work, Al3+ substitution Si4+ in SiO2 by high-temperature sintering to create hole traps to obtain the acceptor-doped fillers Si1-0.75xAlxO2 (SA (x mol%)), and polyimide (PI) dielectric containing SA fillers with different contents were synthesized using in-situ polymerization. The hole traps in the fillers modulate the electrical behavior of the polymer dielectric, thereby significantly increasing the dielectric constant and breakdown strength by modulating the polarization behavior and capture carriers. Among them, the dielectric constant of the 1.25 vol% SA (1.5 mol%)/PI composite was increased to 3.60 at 1 Hz, and the breakdown strength Eb reached 581.5 kV/mm. This work provides a new synthesis strategy for simultaneously achieving high insulation and high polarization of polymer dielectric.

Abstract Background Abnormal glycosylation in a variety of cancer types is involved in tumor progression and chemoresistance. Glycosyltransferase C1GALT1, the key enzyme in conversion of Tn antigen to T antigen, is involved in both physiological and pathological conditions. However, the mechanisms of C1GALT1 in enhancing oncogenic phenotypes and its regulatory effects via non-coding RNA are unclear. Methods Abnormal expression of C1GALT1 and its products T antigen in human bladder cancer (BLCA) were evaluated with BLCA tissue, plasma samples and cell lines. Effects of C1GALT1 on migratory ability and proliferation were assessed in YTS-1 cells by transwell, CCK8 and colony formation assay in vitro and by mouse subcutaneous xenograft and trans-splenic metastasis models in vivo. Dysregulated circular RNAs (circRNAs) and microRNAs (miRNAs) were profiled in 3 pairs of bladder cancer tissues by RNA-seq. Effects of miR-1-3p and cHP1BP3 (circRNA derived from HP1BP3) on modulating C1GALT1 expression were investigated by target prediction program, correlation analysis and luciferase reporter assay. Functional roles of miR-1-3p and cHP1BP3 on migratory ability and proliferation in BLCA were also investigated by in vitro and in vivo experiments. Additionally, glycoproteomic analysis was employed to identify the target glycoproteins of C1GALT1. Results In this study, we demonstrated upregulation of C1GALT1 and its product T antigen in BLCA. C1GALT1 silencing suppressed migratory ability and proliferation of BLCA YTS-1 cells in vitro and in vivo. Subsets of circRNAs and miRNAs were dysregulated in BLCA tissues. miR-1-3p, which is reduced in BLCA tissues, inhibited transcription of C1GALT1 by binding directly to its 3′-untranslated region (3′-UTR). miR-1-3p overexpression resulted in decreased migratory ability and proliferation of YTS-1 cells. cHP1BP3 was upregulated in BLCA tissues, and served as an miR-1-3p “sponge”. cHP1BP3 was shown to modulate migratory ability, proliferation, and colony formation of YTS-1 cells, and displayed tumor-suppressing activity in BLCA. Target glycoproteins of C1GALT1, including integrins and MUC16, were identified. Conclusions This study reveals the pro-metastatic and proliferative function of upregulated glycosyltransferase C1GLAT1, and provides preliminary data on mechanisms underlying dysregulation of C1GALT1 via miR-1-3p / cHP1BP3 axis in BLCA.

In this paper, a Ni coating was deposited on the surface of the A356 aluminum alloy by high velocity oxygen fuel spraying to improve the performance of the AZ91D magnesium/A356 aluminum bimetal prepared by a compound casting. The effects of the Ni coating as well as its thickness on microstructure and mechanical properties of the AZ91D/A356 bimetal were systematically researched for the first time. Results demonstrated that the Ni coating and its thickness had a significant effect on the interfacial phase compositions and mechanical properties of the AZ91D/A356 bimetal. The 10µm's Ni coating cannot prevent the generation of the Al-Mg intermetallic compounds (IMCs) at the interface zone of the AZ91D/A356 bimetal, while the Ni coating with the thickness of 45 µm and 190 µm can avoid the formation of the Al-Mg IMCs. When the Ni coating was 45 µm, the Ni coating disappeared and transformed into Mg-Mg2Ni eutectic structures+Ni2Mg3Al particles at the interface zone. With a thickness of 190µm's Ni coating, part of the Ni coating remained and the interface layer was composed of the Mg-Mg2Ni eutectic structures+ Ni2Mg3Al particles, Mg2Ni layer, Ni solid solution (SS) layer, Al3Ni2 layer, Al3Ni layer and sporadic Al3Ni+Al-Al3Ni eutectic structures from AZ91D side to A356 side in sequence. The interface layer consisting of the Mg-Ni and Al-Ni IMCs obtained with the Ni coating had an obvious lower hardness than the Al-Mg IMCs. The shear strength of the AZ91D/A356 bimetal with a Ni coating of 45 µm thickness enhanced 41.4% in comparison with that of the bimetal without Ni coating, and the fracture of the bimetal with 45µm's Ni coating occurred between the Mg matrix and the interface layer with a mixture of brittle fracture and ductile fracture.

Chronic endometritis (CE) has been considered to reduce uterine receptivity and negatively affect reproductive outcomes for in vitro fertilization-embryo transfer (IVF-ET) patients, especially for people undergoing recurrent implantation failure (RIF). To investigate the effects of antibiotic and platelet-rich plasma (PRP) therapy on pregnancy outcomes following frozen-thawed embryo transfer (FET) in RIF patients with CE, endometrial specimens of 327 patients with RIF obtained by endometrial scratching during mid-luteal phase were immunostained by multiple myeloma oncogene-1 (Mum-1)/syndecan-1 (CD138). RIF patients with CE were given antibiotics and PRP treatment. According to the Mum-1+/CD138+ plasmacytes after treatment, patients were divided into persistent weak positive CE (+) group, CE (−) group and non-CE group. FET was performed and the basic characteristics and pregnancy outcomes of patients in three groups were compared. Among 327 RIF patients, 117 patients were complicated with CE, the prevalence was 35.78%. The prevalence of strong positive was 27.22% and that of weak positive was 8.56%. 70.94% patients with CE converted to negative after treatment. There was no significant difference in the basic characteristics, including age, BMI, AMH, AFC, infertility years, infertility types, number of previous transplant cycles, endometrial thickness on transplantation day and number of transplanted embryos (p > 0.05); The positive rate of hCG, clinical pregnancy rate and implantation rate in CE (−) group were significantly increased compared with the weak CE (+) group and non-CE group (p < .01), and the live birth rate also improved (p < .05). Whereas, the rate of early abortion in CE (−) group was 12.70%, which was higher than that in weak CE (+) group and non-CE group (p < .05). After multivariate analysis, number of previous failed cycles and CE remained independent factors associated with live birth rate, while only CE remained to be the independent factor of clinical pregnancy rate. It is recommended to perform CE-related examination for patients with RIF. Antibiotic and PRP treatment can significantly improve pregnancy outcomes of patients with CE negative conversion in FET cycle.

A simple mechanical vibration was used to enhance interface bonding of the Al/Mg bimetallic composites produced by a novel lost foam compound casting in this study. The effect of vibration time on interfacial microstructure and mechanical properties of the Al/Mg bimetallic composites was investigated. The results show that the vibration time had a significant effect on the interfacial microstructure and mechanical properties of the Al/Mg bimetallic composites. With the increase of the vibration time, the cooling rate during the solidification was increased, and the thickness of intermetallic compounds (IMCs) layer at the interface of the Al/Mg bimetallic composites was decreased. This resulted in the decrease of A3Mg2 and Al12Mg17 brittle phases, and the Mg2Si phase at the interface was refined with a distribution change from agglomeration to dispersion. When the vibration time was 300 s, the vibration fully affected the formation and solidification process of the IMCs layer of the Al/Mg bimetallic composites, and had an obvious effect on the reduction of the brittle phases as well as the improvement of the size and distribution of the Mg2Si phase. As a result, the shear strength of the Al/Mg bimetallic composites was the highest, reaching 47.49 MPa, which was 51% higher than that of the Al/Mg bimetallic composites without vibration.

This study aims to enhance the stability and bioavailability of nuciferine (NF) and epigallocatechin-3-gallate (EGCG) by loading NF into liposomes and then incorporating the liposomes and EGCG into porous microgels (NFEG-microgel) prepared with chitosan and proanthocyanidin. Analysis of particle size (0.5–3.0 μm), electron microscopy, rheology, stability, and simulated gastrointestinal release confirmed that the prepared microgels had high encapsulation rate and good stability and release characteristics. Intervention experiments were performed by orally administering NFEG-microgel to high-fat diet rats to evaluate its efficacy and regulatory mechanism for blood lipid metabolism. NFEG-microgel intervention significantly reduced the body weight and serum lipid level, and the mechanism was related to the expression regulation of key genes involved in lipid metabolism and miRNAs (miR-126a-5p and miR-30b-5p) in serum extracellular vesicles. In addition, NFEG-microgel improved the diversity of gut microbiota by enriching short-chain fatty acids (SCFA)-producing bacteria and reducing harmful bacteria, suggesting that it can ameliorate lipid metabolism by regulating the intestinal flora community in rats.

Natural polysaccharides are macromolecular substances with great potential owing to their wide biological activity and low toxicity. However, not all polysaccharides have significant pharmacodynamic activity; hence, appropriate chemical modification methods can be selected according to the unique structural characteristics of polysaccharides to assist in enhancing and promoting the presentation of their biological activities. This review summarizes research progress on modified polysaccharides, including common chemical modification methods, the change in biological activity following modification, and the factors affecting the biological activity of chemically modified polysaccharides. At the same time, the difficulties and challenges associated with the structural modification of natural polysaccharides are also outlined in this review. Thus, research on polysaccharide structure modification is critical for improving the development and utilization of sugar products.

BackgroundBreast cancer is one of the most important diseases in women around the world. Glycosylation modification correlates with carcinogenesis and roles of glycogenes in the clinical outcome and immune microenvironment of breast cancer are unclear.MethodsA total of 1297 breast cancer and normal cases in the TCGA and GTEx databases were enrolled and the transcriptional and survival information were extracted to identify prognostic glycogenes using Univariate Cox, LASSO regression, Multivariate Cox analyses and Kaplan-Meier method. The immune infiltration pattern was explored by the single sample gene set enrichment method. The HLA and immune checkpoint genes expression were also compared in different risk groups. The expressions of a glycogene MGAT5 as well as its products were validated by immunohistochemistry and western blotting in breast cancer tissues and cells.ResultsA 19-glycogene signature was identified to separate breast cancer patients into high- and low-risk groups with distinct overall survival rates (P < 0.001). Compared with the high-risk group, proportion of naive B cells, plasma cells and CD8+ T cells increased in the low-risk group (P < 0.001). Besides, expressions of HLA and checkpoint genes, such as CD274, CTLA4, LAG3 and TIGIT3, were upregulated in low-risk group. Additionally, highly expressed MGAT5 was validated in breast cancer tissues and cells. Downstream glycosylation products of MGAT5 were all increased in breast cancer.ConclusionsWe identified a 19-glycogene signature for risk prediction of breast cancer patients. Patients in the low-risk group demonstrated a higher immune infiltration and better immunotherapy response. The validation of MGAT5 protein suggests a probable pathway and target for the development and treatment of breast cancer.

We investigated the effects of nuciferine rich in Lotus leaf on the amelioration of hepatic steatosis and dyslipidemia of hyperlipidemic rats, and explored the underlying mechanism on miRNAs and genes expression. Serum extracellular vesicles (EVs) from rats were prepared and characterized, and interactions between miRNAs and target mRNAs were validated in 293T cell line with the double luciferase reporter gene assay. Results showed that nuciferine significantly induced the expression of PPARα, ABCA1, CYP7A1, LXRα in liver and ABCG5 in intestine, while NPC1L1 expression was markedly reduced. In vitro, double luciferase reporter assays showed that miRNA-764-5p, miRNA-758-3p, and miRNA-126-5p interacted with the target mRNAs of PPARα, ABCA1, and CYP7A1, respectively. And the effect of nuciferine on lipid metabolism in rats was related to regulate intestinal absorption and serum EVs miRNAs. These miRNAs were able to reduce lipid levels by targeting lipid metabolism genes and up-regulating PPARα-LXRα-ABCA1 pathway and CYP7A1 expression.

This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar (Acipenser baerii/Acipenser gueldenstaedtii/Acipenser schrenckii/Huso dauricus/Huso huso). Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.

Abstract Background Sialic acids are widely distributed in animal tissues, and aberrantly expressed in a variety of cancer types. High expression of sialic acid contributes to tumor aggressiveness by promoting cell proliferation, migration, angiogenesis, and metastasis. Sialidases are responsible for removal of sialic acids from glycoproteins and glycolipids. Methods N-glycomics of bladder cancer cells were detected by MALDI-TOF mass spectrometry. Sialic acid modification in bladder cancer tissue was determined by lectin blot. The down-regulation of NEU1 in bladder cancer cells was determined by high resolution liquid chromatography mass spectrometry (HR LC-MS). The effects of sialidase NEU1 expression on proliferation and apoptosis of human bladder cancer cells were examined by western blot, RT-PCR, confocal imaging and flow cytometry. Moreover, the function of sialic acids on fibronectin-integrin α5β1 interaction were assayed by immunoprecipitation and ELISA. The importance of NEU1 in tumor formation in vivo was performed using BALB/c-nu mice. Expression of NEU1 in primary human bladder cancer tissue samples was estimated using bladder cancer tissue microarray. Results (1) Downregulation of NEU1 was primarily responsible for aberrant expression of sialic acids in bladder cancer cells. (2) Decreased NEU1 expression was correlated with bladder cancer progression. (3) NEU1 overexpression enhanced apoptosis and reduced proliferation of bladder cancer cells. (4) NEU1 disrupted FN-integrin α5β1 interaction and deactivated the Akt signaling pathway. (5) NEU1 significantly suppressed in vivo tumor formation in BALB/c-nu mice. Conclusions Our data showed that NEU1 inhibited cancer cell proliferation, induced apoptosis, and suppressed tumor formation both in vitro and in vivo, by disrupting interaction of FN and integrin β1 and inhibiting the Akt signaling pathway. Our observations indicate that NEU1 is an important modulator of the malignant properties of bladder cancer cells, and is a potential therapeutic target for prognosis and treatment of bladder cancer. Video Abstract Graphical abstract

Small extracellular vesicles (sEVs) are a type of membrane structure secreted by cells, which are involved in physiological and pathological processes by participating in intercellular communication. Glycosphingolipids (GSLs) are enriched in sEV and can be delivered to recipient cells. In this study, we found that overexpression of B3GALT4, the glycosyltransferase responsible for ganglioside GM1 synthesis, can induce the epithelial–mesenchymal transition (EMT) process in MCF-10A cells. Moreover, GM1 was verified to be presented on sEV from breast cancer cells. Overexpression of B3GALT4 resulted in elevated vesicular GM1 levels and increased sEV secretion in breast cancer cells. Proteomic analysis revealed that eleven sEV secretion-related proteins were differentially expressed, which might contribute to the altered sEV secretion. Of the identified proteins, 15 oncogenic differentially expressed proteins were documented to be presented in sEV. With the treatment of GM1-enriched sEV from breast cancer cells, the EMT process was induced in recipient non-tumorigenic epithelial MCF-10A cells. Our findings demonstrated that GM1-enriched sEVs derived from breast cancer cells induced the EMT process of recipient cells, which might provide essential information on the biological function of vesicular GM1.

Travel entail change in geography and diet, both of which are known as determinant factors in shaping the human gut microbiome. Additionally, altered gut microbiome modulates immunity, bringing about health implications in humans. To explore the effects of the mid-term travel on the gut microbiome, we generated 16S rRNA gene and metagenomic sequencing data from longitudinal samples collected over six months. We monitored dynamic trajectories of the gut microbiome variation of a Chinese volunteer team (VT) in their whole journey to Trinidad and Tobago (TAT). We found gut microbiome resilience that VT’s gut microbial compositions gradually transformed to the local TAT’s enterotypes during their six-month stay in TAT, and then reverted to their original enterotypes after VT’s return to Beijing in one month. Moreover, we identified driven species in this bi-directional plasticity that could play a role in immunity modulation, as exemplified by Bacteroides dorei that attenuated atherosclerotic lesion formation and effectively suppressed proinflammatory immune response. Another driven species P. copri could play a crucial role in rheumatoid arthritis pathogenesis, a chronic autoimmune disease. Carbohydrate-active enzymes are often implicated in immune and host-pathogen interactions, of which glycoside hydrolases were found decreased but glycosyltransferases and carbohydrate esterases increased during the travel; these functions were then restored after VT’ returning to Beijing. Furthermore, we discovered these microbial changes and restoration were mediated by VT people’s dietary changes. These findings indicate that half-year travel leads to change in enterotype and functional patterns, exerting effects on human health. Microbial intervention by dietary guidance in half-year travel would be conducive to immunity modulation for maintaining health.

Evaluating tumor development is of great importance for clinic treatment and therapy. It has been known that the amounts of sialic acids on tumor cell membrane surface are closely associated with the degree of cancerization of the cell. So, in this work, cellular interface supported CRISPR/Cas trans-cleavage has been explored for electrochemical simultaneous detection of two types of sialic acids, i.e., N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac). Specifically, PbS quantum dot-labeled DNA modified by Neu5Gc antibody is prepared to specifically recognize Neu5Gc on the cell surface, followed by the binding of Neu5Ac through our fabricated CdS quantum dot-labeled DNA modified by Sambucus nigra agglutinin. Subsequently, the activated Cas12a indiscriminately cleaves DNA, resulting in the release of PbS and CdS quantum dots, both of which can be simultaneously detected by anodic stripping voltammetry. Consequently, Neu5Gc and Neu5Ac on cell surface can be quantitatively analyzed with the lowest detection limits of 1.12 cells/mL and 1.25 cells/mL, respectively. Therefore, a ratiometric electrochemical method can be constructed for kinetic study of the expression and hydrolysis of Neu5Gc and Neu5Ac on cell surface, which can be further used as a tool to identify bladder cancer cells at different development stages. Our method to evaluate tumor development is simple and easy to be operated, so it can be potentially applied for the detection of tumor occurrence and development in the future.

Abnormally high expression of aryl hydrocarbon receptor (AhR) has been implicated in dedifferentiation of radioiodine-refractory papillary thyroid cancer (RR-PTC). This study aimed to evaluate the differentiation effect of AhR antagonist in PTC, and to explore the potential mechanism of it. Results showed that AhR antagonists promoted differentiation of PTC, as shown as increase in 125I uptake and Na/I symporter (NIS) expression level. CircRNA microarray in K1 cells treated with StemRegenin 1(SR1) revealed that hsa_circ_0006741 (circSH2B3) was down-regulated in SR1 treated K1 cells. Downregulation of circSH2B3 increased 125I uptake and NIS expression levels. CircSH2B3 acted as an endogenous sponge of hsa-miR-4640-5p and modulated IGF2BP2 expression. IGF2BP2 overexpression induced dedifferentiation of PTC, while silencing IGF2BP2 accelerated differentiation of PTC cells. Rescue studies showed that the dedifferentiation activity of AhR was modulated by the circSH2B3/miR-4640-5p/IGF2BP2 axis. Our findings confirmed for the first time that AhR antagonists promote differentiation of PTC via inhibiting the circSH2B3/miR-4640-5p/IGF2BP2 axis, offering a novel therapeutic approach and a potential marker for differentiation of PTC.

Abstract. Background:. Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism. Methods:. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance. Results:. RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t = 16.55, P

Objective To investigate the application of neuroendoscopy and curative effect of lateral skull base surgery via transcranial approach. Methods Clinical data of 142 cases undergoing endoscopic lateral skull base surgeries via transcranial approach from July 2015 to July 2018 were retrospectively analyzed. There were 32 cases of primary hemifacial spasm, 56 cases of primary trigeminal neuralgia, 2 cases of primary glossopharyngeal neuralgia, 15 cases of epidermoid cyst, 14 cases of acoustic neuroma, 3 cases of trigeminal schwannoma, 18 cases of pontocerebellar trigone meningioma, and 2 cases of jugular foramen schwannoma. Among them, 90 cases (32 cases of primary hemifacial spasm, 56 cases of primary trigeminal neuralgia and 2 cases of primary glossopharyngeal neuralgia) underwent endoscopic microvascular decompression (MVD) via transcranial approach, and 52 cases (15 cases of epidermoid cyst, 14 cases of acoustic neuroma, 3 cases of trigeminal schwannoma, 18 cases of pontocerebellar trigone meningioma, and 2 cases of jugular foramen schwannoma) underwent endoscopic removal of lateral skull base tumors via transcranial approach. Results All the operations were performed under endoscopy, including 96 cases (67.61%) operated by single hand (the endoscope was held by a pneumatic arm) and the rest 46 cases (32.39%) operated by both hands. The cure rate of MVD was 87.78% (79/90) and the total removal rate of lateral skull base tumors was 90.38% (47/52). The mean follow-up period was (23.46 ± 8.93) months. There was no death or other serious complications. Conclusions The complex lateral skull base surgery via transcranial approach can be performed by neuroendoscope with pneumatic endoscopic fixed arm. It has the advantages of near and multi-angle observation, clear visual field, full exposure and high recognition of nerve and blood vessels. However, the requirements for endoscopic technology, instruments and assistive equipments are high, and it is necessary to receive relevant trainings and experiences in endoscopic surgery. DOI: 10.3969/j.issn.1672-6731.2019.03.008

Cytarabine (Ara-C) has been one of the frontline therapies for clonal hematopoietic stem cell disorders, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but Ara-C resistance often occurs and leads to treatment failure. Exosomal microRNAs (miRNAs, miRs) as small noncoding RNA that play important roles in post-transcriptional gene regulation, can be delivered into recipient cells by exosomes and regulate target genes’ expression. miR92a has been reported to be dysregulated in many cancers, including MDS and AML. However, the effects of exosomal miR92a in hematologic malignancies have not been fully investigated. In this study, qualitative analysis showed the significantly enhanced expression of exosomal miR92a in MDS/AML plasma. Subsequent functional assays indicated that exosomal miR92a can be transported and downregulate PTEN in recipient cells and, furthermore, activate the Wnt/β-catenin signaling pathway and interfere with the Ara-C resistance of receipt MDS/AML cells in vitro and in vivo. Altogether, our findings offer novel insights into plasma exosomal miR92a participating in Ara-C resistance in MDS/AML and we propose miR92a as a potential therapeutic target for MDS/AML.

Hepatocellular carcinoma (HCC) is one of the dominating causes of cancer-related death throughout the world. Treatment options for patients with HCC vary, however, the lack of effective targeted drugs is the major reason for death in advanced HCC patients. In this study, a delivery system based on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) loaded with doxorubicin (Dox) was developed. In this system, we initially erased terminal linked α2–3 and α2–6 sialic acids on the surface of EVs by neuraminidase. The exhibition of galactose (Gal) and N-acetylgalactosamine (GalNAc) residues in treated MSC-EVs can specifically be recognized by asialoglycoprotein receptor (ASGPR) of hepatoma cells. Compared to free Dox and Dox-loaded EVs, desialylated EVs loaded with Dox significantly presented the improved cellular uptake, prioritized targeting efficacy, and had a better inhibiting effect in vitro and in vivo. Overall, the results of the present study of the demonstrated delivery system using desialylated MSC-EVs suggest its therapeutic potential for HCC.

Background: To optimize [18F] 9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) purification via solid-phase extraction (SPE) with combined cartridges to facilitate its widespread clinical application.Methods: A modified SPE purification method, employing Sep-Pak PS-2 and Sep-Pak C18 cartridges, was used for the preparation of 18F-FP-(+)-DTBZ. This method was compared to the purification method of high-pressure liquid chromatography (HPLC) and SPE with one cartridge, following quality control test and positron emission tomography (PET) imaging in healthy volunteers and patients with parkinsn's disease (PD).Results: A SPE purification method integrating Sep-Pak PS-2 and Sep-Pak C18 cartridges was implemented successfully. The retention time of 18F-FP-(+)-DTBZ purified by HPLC, SPE with Sep-Pak PS-2, SPE with Sep-Pak C18, and SPE with combined use of Sep-Pak PS-2 and Sep-Pak C18 cartridges was 8.7, 8.8, 8.7, and 8.9 min, respectively. Fewest impurity peak was detected in 18F-FP-(+)-DTBZ purified by the SPE with combined use of Sep-Pak PS-2 and Sep-Pak C18 cartridges. This modified SPE purification method provided a satisfactory radiochemical yield of 29 ± 1.8% with radiochemical purity >99% and shortened synthesis time to 27 min. The brain uptake of 18F-FP-(+)-DTBZ purified by the modified SPE was comparable to that purified by HPLC in both healthy volunteers and PD patients.Conclusions: A SPE method integrating Sep-Pak PS-2 and Sep-Pak C18 cartridges for purification of 18F-FP-(+)-DTBZ may be highly suited to automatic synthesis for routine clinical applications, as it provides excellent radiochemical purity, high yield as well as operational simplicity.

The inhibitor of growth (ING) family was discovered as the type II tumor suppressors, which regulated the proliferation, apoptosis, differentiation, angiogenesis, metastasis, and invasion of tumor cells through multiple pathways. ING3, a new member of ING family, has been reported to be downregulated in several types of tumors. However, few studies on ING3 in breast cancer have been reported. In this study, we investigated the expression of ING3 and determined its prognostic value in breast cancer. The immunohistochemistry was performed to evaluate the expression of ING3 in tissue microarrays (TMA) including breast cancer tissues (n=211) and normal breast tissues (n=50). In normal breast tissues, ING3 protein was detected in both the cytoplasm and nucleus. In breast cancer tissues, ING3 protein was principally detected in the cytoplasm. Compared with normal breast tissues, the expression of ING3 in nucleus was remarkably reduced in breast cancer tissues. The downregulated ING3 in nucleus was significantly correlated with clinicopathological characteristics including histological grade, lymph node metastasis, and the status of ER and PR. In HER2 positive-type and triple-negative breast cancer (TNBC) patients, it had the lower rate of nuclear ING3 with high expression than that in luminal-type. Moreover, Kaplan-Meier curves demonstrated that the reduced expression of ING3 in nucleus was correlated with a poorer 5-DFS and 5-OS of breast cancer patients. Importantly, multivariate Cox regression analysis suggested that the reduced expression of ING3 in nucleus was an independent prognostic factor in breast cancer. Our study comprehensively described the expression of ING3 in breast cancer for the first time and proved that it was an independent prognostic predictor of breast cancer, as well as a new idea for study of breast cancer.