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Abstract Background Ferroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms of m6A-related regulators in HCC cell ferroptosis remain unclear. Methods By examining a series of m6A modification enzymes upon ferroptosis induction or inhibition, we identified METTL16 as a novel ferroptotic repressor in HCC cells. The roles of METTL16 on ferroptosis and HCC development were investigated in multiple cell lines, human HCC organoids, subcutaneous xenografts and MYC/Trp53−/− HCC model in hepatocyte-specific Mettl16 knockout and overexpression mice. The underlying mechanism was elucidated with MeRIP/RIP-qPCR, luciferase assay, Co-IP assay and Mass Spectrometry. The clinical significance and relevance were evaluated in human samples. Results High METTL16 expression confers ferroptosis resistance in HCC cells and mouse models, and promotes cell viability and tumor progression. Mechanistically, METTL16 collaborates with IGF2BP2 to modulate SENP3 mRNA stability in an m6A-dependent manner, and the latter impedes the proteasome-mediated ubiquitination degradation of Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF expression facilitates the chelation of free iron and reduces liable iron pool level. SENP3 and LTF are implicated in METTL16-mediated HCC progression and anti-ferroptotic effects both in vivo and in vitro. Clinically, METTL16 and SENP3 expression were positively correlated, and high METTL16 and SENP3 expression predicts poor prognosis in human HCC samples. Conclusions Our study reveals a new METTL16-SENP3-LTF signaling axis regulating ferroptosis and driving HCC development. Targeting this axis is a promising strategy for sensitizing ferroptosis and against HCC.

Abstract The topological photonics plays an important role in the fields of fundamental physics and photonic devices. The traditional method of designing topological system is based on the momentum space, which is not a direct and convenient way to grasp the topological properties, especially for the perturbative structures or coupled systems. Here, we propose an interdisciplinary approach to study the topological systems in real space through combining the information entropy and topological photonics. As a proof of concept, the Kagome model has been analyzed with information entropy. We reveal that the bandgap closing does not correspond to the topological edge state disappearing. This method can be used to identify the topological phase conveniently and directly, even the systems with perturbations or couplings. As a promotional validation, Su–Schrieffer–Heeger model and the valley-Hall photonic crystal have also been studied based on the information entropy method. This work provides a method to study topological photonic phase based on information theory, and brings inspiration to analyze the physical properties by taking advantage of interdisciplinarity. Graphical Abstract

Objective: To investigate the effects of a high-fat diet (HFD) on the gut bacterium Roseburia intestinalis and butyric acid levels, and to assess their impact on ovarian function and epigenetic markers in mice. Methods: A total of 20 female ICR mice aged 4 weeks were randomly assigned to two groups and fed either a control diet (CD) or an HFD for 36 weeks. Post-intervention, ileal contents were analyzed for the quantification of butyric acid using ELISA, while feces were obtained for Roseburia intestinalis expression assessment via qPCR. Histological evaluations of intestinal and ovarian tissues included H&E and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining, alongside immunohistochemical analysis for F4/80, and immunofluorescent detection of Occludin, ZO-1, 5 mC, and H3K36me3. Ovarian health was assessed through follicle counts and morphological evaluations. Statistical analyses were performed using GraphPad Prism 8.0, with P

Abstract Nonreciprocal interlayer coupling is difficult to practically implement in bilayer non-Hermitian topological photonic systems. In this work, we identify a similarity transformation between the Hamiltonians of systems with nonreciprocal interlayer coupling and on-site gain/loss. The similarity transformation is widely applicable, and we show its application in one- and two-dimensional bilayer topological systems as examples. The bilayer non-Hermitian system with nonreciprocal interlayer coupling, whose topological number can be defined using the gauge-smoothed Wilson loop, is topologically equivalent to the bilayer system with on-site gain/loss. We also show that the topological number of bilayer non-Hermitian C6v-typed domain-induced topological interface states can be defined in the same way as in the case of the bilayer non-Hermitian Su–Schrieffer–Heeger model. Our results show the relations between two microscopic provenances of the non-Hermiticity and provide a universal and convenient scheme for constructing and studying nonreciprocal interlayer coupling in bilayer non-Hermitian topological systems. This scheme is useful for observation of non-Hermitian skin effect in three-dimensional systems. Graphical Abstract

Abstract Background Ubiquitin-specific protease 32 (USP32) is a highly conserved gene that promotes cancer progression. However, its role in hepatocellular carcinoma (HCC) is not well understood. The aim of this project is to explore the clinical significance and functions of USP32 in HCC. Methods The expression of USP32 in HCC was evaluated using data from TCGA, GEO, TISCH, tissue microarray, and human HCC samples from our hospital. Survival analysis, PPI analysis and GSEA analysis were performed to evaluate USP32-related clinical significance, key molecules and enrichment pathways. Using the ssGSEA algorithm and TIMER, we investigated the relationships between USP32 and immune infiltrates in the TME. Univariate and multivariate Cox regression analyses were then used to identify key USP32-related immunomodulators and constructed a USP32-related immune prognostic model. Finally, CCK8, transwell and colony formation assays of HCC cells were performed and an HCC nude mouse model was established to verify the oncogenic role of USP32. Results USP32 is overexpressed in HCC and its expression is an independent predictive factor for outcomes of HCC patients. USP32 is associated with pathways related to cell behaviors and cancer signaling, and its expression is significantly correlated with the infiltration of immune cells in the TME. We also successfully constructed a USP32-related immune prognostic model using 5 genes. Wet experiments confirmed that knockdown of USP32 could repress the proliferation, colony formation and migration of HCC cells in vitro and inhibit tumor growth in vivo. Conclusion USP32 is highly expressed in HCC and closely correlates with the TME of HCC. It is a potential target for improving the efficacy of chemotherapy and developing new strategies for targeted therapy and immunotherapy in HCC.

The cystathionine-β-synthase (CBS) domain is present in the proteins of all living organisms and functions as an energy sensor, regulating protein activity through the binding capacity of its adenosine ligands. The role of the CBS gene in plant growth and development, as well as tolerance to abiotic stresses, remains largely unknown, especially in grapevine. In our study, 32 members of the CBS gene family were obtained that were distributed on 15 chromosomes. The results of the structural and evolutionary tree analyses indicated that the VvCBS gene family exhibits diverse intron-exon patterns and highly conserved motifs. Furthermore, the phylogenetic classification of the VvCBS genes revealed the presence of three subfamilies. Subcellular localization analyses showed that the VvCBS genes are mainly located in the plasma membrane region. The secondary structure of the VvCBS protein mainly consists of α-helices, extended strands, β-turns, and random coils. The VvCBS gene family exhibited four co-linear gene pairs, while the numbers for Arabidopsis thaliana and rice were 21 and 7, respectively. The promoter cis-acting element analysis revealed the presence of light-responsive, hormone-responsive, stress-responsive, and growth- and development-related elements in the VvCBS family. The expression characterization demonstrated that 12 VvCBS genes exhibited high expression levels in all grape tissues. Additionally, the RT-qPCR expression analyses showed that the 32 VvCBS exhibited different responses to a variety of abiotic stresses (cold, drought, salt), suggesting that they were functionally differentiated. VvCBS27 was cloned from ‘Pinot Noir’ of grapevine with a coding sequence of 624 bp. Subcellular localization showed that VvCBS27 protein was mainly located in the cytoplasm, cell membrane, and nucleus. This study lays a foundation for elucidating the function of grape CBS protein.

This study explores fault-tolerant consensus in leader–following heterogeneous multi-agent systems, focusing on actuator failures in uncrewed aerial vehicles (UAVs) and uncrewed ground vehicles (UGVs). An optimization-based fault-tolerant consensus algorithm is proposed. The algorithm utilizes the Euler–Lagrange formula to ensure system consistency under actuator failures, with the Lyapunov stability theory proving the asymptotic stability of the consistency error. The algorithm is applied to heterogeneous multi-agent systems of UAVs and UGVs to derive optimal fault-tolerant consensus control laws for each vehicle type. Simulation experiments give evidence for the feasibility of the proposed control strategy.

Abstract Background Limited data have been used to evaluate the efficacy of immunotherapy in metastatic colorectal cancer (mCRC). Furthermore, potential markers that can be used to identify responding patients and to further improve efficacy have not been fully explored. Methods and Results In our study, we included a total of 97 patients with mCRC, who each received programmed death‐1 (PD‐1) inhibitor‐based combination therapy at our center. All 12 hypermutated patients benefited from immunotherapy, with median progression‐free survival (mPFS) reaching 28.3 months, regardless of liver metastasis. The objective response rate (ORR) of non‐hypermutated patients was 16.5% (14/85), with an mPFS of 4.0 months. For non‐hypermutated patients, multivariate analysis revealed that the combination of liver metastasis and baseline lesion number significantly stratified response and survival. The lesion‐based analysis indicated that the lymph node was the most responsive, followed by the peritoneum and lung, with liver metastasis being the least responsive. None of the patients (0/7) with negative programmed ligand‐1 (PD‐L1) expression responded, and positive PD‐L1 expression may serve as a biomarker (mPFS 5.7 vs. 2.2 months, p = 0.002) that can be used to further guide treatment in non‐hypermutated mCRC with liver metastasis (CRLMs). Conclusion Patients with hypermutated mCRC benefited significantly from immunotherapy, whereas the non‐hypermutated cohort with liver metastasis and numerous lesions showed less benefit. The lesion sites reflected varying levels of efficacy, among which PD‐L1 potentially cooperated to guide the immunotherapy of CRLMs.

Abstract Background Low-grade gliomas (LGG) are a type of brain tumor that can be lethal, and it is essential to identify genes that are correlated with patient prognosis. In this study, we aimed to use CRISPR-cas9 screening data to identify key signaling pathways and develop a genetic signature associated with high-risk, low-grade glioma patients. Methods The study used CRISPR-cas9 screening data to identify essential genes correlated with cell survival in LGG. We used RNA-seq data to identify differentially expressed genes (DEGs) related to cell viability. Moreover, we used the least absolute shrinkage and selection operator (LASSO) method to construct a genetic signature for predicting overall survival in patients. We performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the Weighted correlation network analysis (WGCNA). Finally, the study used western blot, qRT-PCR, and IHC to detect the expression of hub genes from signature in clinical samples. Results The study identified 145 overexpressed oncogenes in low-grade gliomas using the TCGA database. These genes were intersected with lethal genes identified in the CRISPR-cas9 screening data from Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct a genetic signature, and the Hippo signaling pathway was found to be the predominantly enriched pathway. The signature effectively distinguished between low- and high-risk patients, with high-risk patients showing a shorter overall survival duration. Differences in hub gene expression were found in different clinical samples, with the protein and mRNA expression of REP65 being significantly up-regulated in tumor cells. The study suggests that the Hippo signaling pathway may be a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including low-grade gliomas. Conclusion Our study identified a novel genetic signature associated with high-risk, LGG patients. We found that the Hippo signaling pathway was significantly enriched in this signature, indicating that it may be a critical regulator of tumor viability and proliferation in LGG. Targeting the Hippo pathway could be an innovative new strategy for treating LGG.

Background. The pineal region represents significant challenges in terms of neurosurgery. Currently, anatomical research that simulates surgery for the endoscopic keyhole approach to the pineal region is lacking. This study aims to summarize the exposure range and operational characteristics of total endoscopic surgery under the four supratentorial and infratentorial keyhole approaches, through rigorous quantitative anatomical research. We also aim to understand the surgical exposure characteristics and surgical feasibility under each approach. Method. Six wet cadaveric head specimens (a total of 12 sides) were subjected to simulated surgery with a keyhole bone window size of approximately 3 × 4 cm. The median endoscopic supracerebellar infratentorial approach (M-ESCITA), the paramedian endoscopic supracerebellar infratentorial approach (PM-ESCITA), the endoscopic occipital transtentorial approach (EOTA), and the endoscopic interhemispheric high occipital transtentorial approach (EHOTA) were used to measure the surgical path depth, maximum distance between the tentorial margins, maximum operable area, operable angle, and relative degree of freedom of each approach. Results. There was no difference in the exposure range of the surgical area. The surgical path of PM-ESCITA was the longest (p

Background: Different RAS/BRAF allele mutations imply distinct biological properties in various solid tumors. Recently, several studies have focused on the predictive and prognostic roles of various RAS/BRAF allele mutations in colorectal cancer (CRC) but the results remain controversial. Methods: Between March 2017 and September 2022, the patients diagnosed as stages I–IV CRC with detailed medical records including next-generation sequencing (NGS) data and clinicopathological follow-up information available at our center were enrolled. Survival data were estimated using the Kaplan–Meier method, and the difference was tested in a log-rank test. Multivariate tests were carried out using Cox models. Results: A total of 1029 CRC patients were included, and the incidence of RAS/BRAF mutation was 58.4%. The hypermutated cohort was defined as patients with microsatellite instability-H or POLE/D mutation. In the non-hypermutational cohort, only KRAS G13D mutation was associated with a higher incidence and inferior disease-free survival in patients with stage I-III CRC. In the cohort of patients with non-hypermutated metastatic colorectal cancer (mCRC), we assessed the risk of various RAS/BRAF allele mutations and subsequently reclassified patients into four groups based on first-line median progression-free survival: wild type (group 1), low-risk RAS /BRAF mutation (group 2, RAS/BRAF mutations other than KRAS G13D/G12V/G12C or BRAF V600E), high-risk RAS mutation (group 3, KRAS G13D/G12V/G12C), and BRAF V600E mutation (group 4). mCRC patients with high-risk RAS mutation could significantly benefit from intensive triplet chemotherapy (hazard ratio, 2.54; 95% confidence interval, 1.36–5.12; p = 0.0091). Conclusion: In the non-hypermutated CRC cohort, the prognostic risk of various RAS/BRAF allele mutations varied between local and metastatic CRC. KRAS G13D mutation tended to be the only prognostic marker for stages I–III CRC; however, KRAS G13D/G12V/G12C mutations collectively defined a high-risk subgroup of mCRC patients with poor prognosis, who would benefit from intensive triplet chemotherapy.

Abstract Background YTHDF2 is one of important readers of N6-methyladenosine (m6A) modification on RNA. Growing evidence implicates that YTHDF2 takes an indispensable part in the regulation of tumorigenesis and metastasis in different cancers, but its biological functions and underlying mechanisms remain elusive in gastric cancer (GC). Aim To investigate the clinical relevance and biological function of YTHDF2 in GC. Results Compared with matched normal stomach tissues, YTHDF2 expression was markedly decreased in gastric cancer tissues. The expression level of YTHDF2 was inversely associated with gastric cancer patients’ tumor size, AJCC classification and prognosis. Functionally, YTHDF2 reduction facilitated gastric cancer cell growth and migration in vitro and in vivo, whereas YTHDF2 overexpression exhibited opposite phenotypes. Mechanistically, YTHDF2 enhanced expression of PPP2CA, the catalytic subunit of PP2A (Protein phosphatase 2A), in an m6A-independent manner, and silencing of PPP2CA antagonized the anti-tumor effects caused by overexpression of YTHDF2 in GC cells. Conclusion These findings demonstrate that YTHDF2 is down-regulated in GC and its down-regulation promotes GC progression via a possible mechanism involving PPP2CA expression, suggesting that YTHDF2 may be a hopeful biomarker for diagnosis and an unrevealed treatment target for GC.

In the original publication [...]

Abstract Background Circulating soluble programmed death ligand 1 (sPD-L1) can negatively regulate T-cell function and serve as a prognostic or predictive marker in a variety of cancers. However, rare studies have evaluated the potential roles of sPD-L1, and no study has estimated its predictive value for the efficacy of immune treatment in colorectal cancer (CRC). Methods Plasma samples from 192 CRC patients were used to estimate correlations between clinicopathological features and sPD-L1, secreted PD-L1 (secPD-L1) and exosomal PD-L1 (exoPD-L1). Baseline and posttreatment sPD-L1 levels were also investigated in 55 patients with metastatic CRC (mCRC) treated with chemotherapy ± targeted therapy and 40 patients with proficient mismatch repair (pMMR) mCRC treated with combination immunotherapy. Both sPD-L1 and secPD-L1 were quantified by enzyme-linked immunosorbent assay, while exoPD-L1 was analyzed using flow cytometry. Results secPD-L1 was the major component and positively correlated with sPD-L1 in CRC, while exoPD-L1 was almost undetectable. Higher levels of sPD-L1 were detected in patients with distant metastasis, especially those with distant lymph node metastasis and tissue combined positive score (CPS) instead of tumor proportion score (TPS). Chemotherapy or targeted therapy did not significantly impact sPD-L1 concentration. Progressive disease on combination immunotherapy was associated with an increase in sPD-L1 level, whereas no significant change was observed in patients with durable clinical benefit. Conclusion sPD-L1 mainly consisted of secPD-L1, and its level was higher in patients with distant metastasis, especially distant lymph node metastasis and positive CPS. sPD-L1 is a potential dynamic marker to identify rapid progression on combination immunotherapy and avoid ineffective treatment for pMMR CRC.

Abstract Mammalian WNK kinases (WNKs) are serine/threonine kinases that contain four members, WNK1–4. They function to maintain ion homeostasis and regulate blood pressure in mammals. Recent studies have revealed that the dysregulation of WNKs contributes to tumor growth, metastasis, and angiogenesis through complex mechanisms, especially through phosphorylating kinase substrates SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1). Here, we review and discuss the relationships between WNKs and several key factors/biological processes in cancer, including ion channels, cation chloride cotransporters, sodium bicarbonate cotransporters, signaling pathways, angiogenesis, autophagy, and non-coding RNAs. In addition, the potential drugs for targeting WNK-SPAK/OSR1 signaling have also been discussed. This review summarizes and discusses knowledge of the roles of WNKs in cancer, which provides a comprehensive reference for future studies.

Abstract Sorafenib is a classical targeted drug for the treatment of advanced hepatocellular carcinoma (HCC), but intrinsic resistance severely limited its therapeutic effects. In the present study, we aimed to identify crucial genes in HCC cells that affect sorafenib resistance by a CRISPR/Cas9 genome-scale screening. The results indicated that the deficiency of miR-15a and miR-20b contributed to sorafenib resistance, whereas exogenous expression of miR-15a and miR-20b enhanced sorafenib sensitivity of HCC cells by cell viability, colony formation, and flow cytometry analyses. Further analyses revealed that cell division cycle 37 like 1 (CDC37L1) as a common target of miR-15a and 20b, was negatively regulated by the two miRNAs and could enhance sorafenib resistance of HCC cells in vitro and in vivo. Mechanistically, CDC37L1, as a cochaperone, effectively increased the expression of peptidylprolyl isomerase A (PPIA) through strengthening the binding between heat shock protein 90 (HSP90) and PPIA. The results from immunohistochemical staining of a HCC tissue microarray revealed a positive association between CDC37L1 and PPIA expression, and high expression of CDC37L1 and PPIA predicted worse prognosis of HCC patients after sorafenib therapy. Taken together, our findings reveal crucial roles of miR-15a, miR-20b, CDC37L1, and PPIA in sorafenib response of HCC cells. These factors may serve as therapeutic targets and predict prognosis for HCC treated with sorafenib.

Abstract UHMK1, a serine/threonine kinase with a U2AF homology motif, is implicated in RNA processing and protein phosphorylation. Increasing evidence has indicated its involvement in tumorigenesis. However, it remains to be elucidated whether UHMK1 plays a role in the development of colorectal cancer (CRC). Here, we demonstrated that UHMK1 was frequently upregulated in CRC samples compared with adjacent normal tissue and high expression of UHMK1 predicted poor outcomes. Knockdown of UHMK1 by siRNAs restrained CRC cell proliferation and increased oxaliplatin sensitivity, whereas overexpression of UHMK1 promoted CRC cell growth and oxaliplatin resistance, suggesting that UHMK1 plays important oncogenic roles in CRC. Mechanistically, we showed that UHMK1 had a significant effect on IL6/STAT3 signaling by interacting with STAT3. The interaction of UHMK1 with STAT3 enhanced STAT3 activity in regulating gene transcription. Furthermore, we found that STAT3 could in turn transcriptionally activate UHMK1 expression in CRC cells. The complementary experiments for cell growth and oxaliplatin resistance indicated the interdependent relationship between UHMK1 and STAT3. Thus, these collective findings uncovered a new UHMK1/STAT3 positive feedback regulatory loop contributing to CRC development and chemoresistance.

Tumor-associated macrophages (TAMs) exert integrated effects in all aspects of tumor progression, including tumor cell proliferation, angiogenesis, invasion, and metastasis. Recently, considerable preclinical and clinical trials have demonstrated that TAM-targeted therapy is an effective antitumor therapeutic approach, especially as a complementary strategy in combination with conventional chemotherapy, radiotherapy, or emerging immunotherapy. Here, we review all of the current clinical trials targeting TAMs worldwide up to May 2021 and highlight instances of the synergetic therapeutic efficacy of TAM-targeted combined therapeutic strategies. In total, 606 clinical trials were conducted, including 143 tested products. There has been explosive growth in macrophage-targeted therapy around the world during the past decade. Most trials were at early phase, and two-thirds used macrophage-targeting therapy as part of a combination approach. The most common combination is that of traditional chemotherapy with TAM-targeted therapy, followed by immune checkpoint inhibitors and targeted drugs. TAM-targeted therapeutic approaches are a newly emerging but rapidly developing area of anticancer therapy, especially as a combinatorial therapeutic approach. Further investigation of promising combination strategies will pave the way to more effective anticancer therapies.

IntroductionTargetable alterations such as BRAFV600E mutation and NTRK fusion are enriched in microsatellite instability-high (MSI-H) colorectal cancer (CRC). MSI-H with targetable alterations (MSI-H altered) might present unique opportunities for both targeted therapy and immunotherapy. We systematically evaluated the molecular characteristics and immune-related features of MSI-H altered and MSI-H without targetable alterations (MSI-H wt) CRC patients in our study.MethodsAmong 1938 continuously enrolled CRC patients, 126 patients with MSI-H status (6.50%) were included in this retrospective study. Genomic and transcriptomic data were investigated by next-generation sequencing (NGS) and gene expression profiling (GEP), respectively.ResultsBRAFV600E, NTRK1, and FGFR2 mutations were the most frequent targetable alterations in MSI-H CRC patients. The MSI-H altered phenotype was significantly associated with older age (p< 0.001), right side (p=0.024) and females (p= 0.036). No lynch syndrome (LS) patients were identified in MSI-H altered group. The tumor mutational burden (TMB), and tumor neoantigen burden (TNB) of MSI-H altered and wt subgroups were comparable (p

BackgroundEmergence agitation (EA) is common in patients after general anesthesia (GA) and is associated with poor outcomes. Patients with thoracic surgery have a higher incidence of EA compared with other surgery. This study aimed to investigate the impact of pre-anesthetic butorphanol infusion on the incidence of EA in patients undergoing thoracic surgery with GA.Materials and methodsThis prospective randomized controlled trial (RCT) was conducted in 20 tertiary hospitals in China. A total of 668 patients undergoing elective video-assisted thoracoscopic lobectomy/segmentectomy for lung cancer were assessed for eligibility, and 620 patients were enrolled. In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. Patients in the intervention group received butorphanol 0.02 mg/kg 15 min before induction of anesthesia. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of EA after 5 min of extubation, and EA was evaluated using the Riker Sedation-Agitation Scale (RSAS). The incidence of EA was determined by the chi-square test, with a significance of P < 0.05.ResultsIn total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. The incidence of EA 5 min after extubation was lower with butorphanol treatment: 9.8% (29 of 296) vs. 24.5% (75 of 306) in the control group (P = 0.0001). Patients who received butorphanol had a lower incidence of drug-related complications (including injecting propofol pain and coughing with sufentanil): 112 of 296 vs. 199 of 306 in the control group (P = 0.001) and 3 of 296 vs. 35 of 306 in the control group (P = 0.0001).ConclusionThe pre-anesthetic administration of butorphanol reduced the incidence of EA after thoracic surgery under GA.Clinical trial registration[http://www.chictr.org.cn/showproj.aspx?proj=42684], identifier [ChiCTR1900025705].

With the accelerated growth of the UAV industry, researchers are paying close attention to the flight safety of UAVs. When a UAV loses its GPS signal or encounters unusual conditions, it must perform an emergency landing. Therefore, real-time recognition of emergency landing zones on the ground is an important research topic. This paper employs a semantic segmentation approach for recognizing emergency landing zones. First, we created a dataset of UAV aerial images, denoted as UAV-City. A total of 600 UAV aerial images were densely annotated with 12 semantic categories. Given the complex backgrounds, diverse categories, and small UAV aerial image targets, we propose the STDC-CT real-time semantic segmentation network for UAV recognition of emergency landing zones. The STDC-CT network is composed of three branches: detail guidance, small object attention extractor, and multi-scale contextual information. The fusion of detailed and contextual information branches is guided by small object attention. We conducted extensive experiments on the UAV-City, Cityscapes, and UAVid datasets to demonstrate that the STDC-CT method is superior for attaining a balance between segmentation accuracy and inference speed. Our method improves the segmentation accuracy of small objects and achieves 76.5% mIoU on the Cityscapes test set at 122.6 FPS, 68.4% mIoU on the UAVid test set, and 67.3% mIoU on the UAV-City dataset at 196.8 FPS on an NVIDIA RTX 2080Ti GPU. Finally, we deployed the STDC-CT model on Jetson TX2 for testing in a real-world environment, attaining real-time semantic segmentation with an average inference speed of 58.32 ms per image.

Simian retrovirus subtype 8 (SRV-8) infections have been reported in cynomolgus monkeys (Macaca fascicularis) in China and America, but its pathogenicity and immunogenicity are rarely reported. In this work, the SRV-8-infected monkeys were identified from the monkeys with anemia, weight loss, and diarrhea. To clarify the impact of SRV-8 infection on cynomolgus monkeys, infected monkeys were divided into five groups according to disease progression. Hematoxylin (HE) staining and viral loads analysis showed that SRV-8 mainly persisted in the intestine and spleen, causing tissue damage. Additionally, the dynamic variations of blood routine indexes, innate and adaptive immunity, and the transcriptomic changes in peripheral blood cells were analyzed during SRV-8 infection. Compared to uninfected animals, red blood cells, hemoglobin, and white blood cells were reduced in SRV-8-infected monkeys. The percentage of immune cell populations was changed after SRV-8 infection. Furthermore, the number of hematopoietic stem cells decreased significantly during the early stages of SRV-8 infection, and returned to normal levels after antibody-mediated viral clearance. Finally, global transcriptomic analysis in PBMCs from SRV-8-infected monkeys revealed distinct gene expression profiles across different disease stages. In summary, SRV-8 infection can cause severe pathogenicity and immune disturbance in cynomolgus monkeys, and it might be responsible for fatal virus-associated immunosuppressive syndrome.

Abstract Background To explore central nervous system (CNS) involvement in this disease, from the perspectives of diagnosis, treatment, and misdiagnosis Methods Twenty-eight patients with CNS echinococcosis were included in this retrospective study, including 18 males (64.3%) and 10 (35.7%) females. The average age of all the patients were 23.5 years (ranged 4–60 years). Twenty-three (23) patients (82.1%) received the first surgical resection in our hospital. Five (5) patients (17.9%) gave up surgical treatment for multiple-organ hydatidosis and previous surgery history at other hospitals, and albendazole was applied for a long-term (3–6 months) adjunct therapy for the 5 patients. The average follow-up time was 8 years. Results For the 28 patients, 23 cases received surgical treatments, and the diagnosis was confirmed by pathological examinations. The diagnosis of 4 cases of brain echinococcosis and 2 cases of spinal cord echinococcosis could not be confirmed, resulting in a misdiagnosis rate of 21.4% (6/28). For the pathological examination, a total of 17 cases were infected with Echinococcus granulosus (including 2 cases of spinal cord echinococcosis), and 6 cases were infected with Echinococcus alveolaris. Conclusion The diagnosis should be specifically considered in endemic regions. The clinical features of CNS hydatidosis were intracranial space-occupying lesions. For the treatment, the surgical removal of cysts should be necessary. In addition, the adjuvant therapy with drug and intraoperative prophylaxis is also suggested. The misdiagnosis may have resulted from atypical clinical features and radiographic manifestations, as well as the accuracy of hydatid immunologic test.

BackgroundEndoscopic submucosal dissection (ESD) is technically difficult with high rates of complications, such as perforation and bleeding. We aimed to explore the safety and cutting efficiency of a novelly devised bipolar knife for ESD procedure.MethodsTaking a traditional monopolar knife as a reference, the safety and feasibility of the novel bipolar knife were evaluated by an animal experiment and a human study. Furthermore, we assessed the usefulness and advantage of this novel bipolar knife by using the finite element method.ResultsA porcine experiment confirmed that there was no significant difference in wound size and cutting speed between the monopolar and bipolar knives. The thermal damage and histopathological scores produced by the two knives were similar. In addition, the porcine experiment and patients' study identified that the incidence of postoperative complications, such as bleeding, perforation, and infection, had no statistical difference between the monopolar and bipolar groups. Finally, the finite element model showed that the length and depth of thermal damage caused by the bipolar knife were, respectively, 102.77–117.98% and 80.87–84.53% of those caused by the monopolar knife at the same power.ConclusionThe novel bipolar knife was theoretically safer than the monopolar knife and, at least, was confirmed not inferior to the monopolar knife in operability and cutting efficiency. Thus, the novel bipolar knife can be an alternative device choice for ESD.

Abstract Background Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC. Methods NELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections. Results NELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other. Conclusion Our findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.

In this paper, cooperative control and optimal control methods are used for the formation control of mixed-order heterogeneous multi-agent systems. The system consists of unmanned aerial vehicles (UAVs), unmanned surface vehicles (USVs), and unmanned underwater vehicles (UUVs). The system is represented in a state space using a block Kronecker product. The static and dynamic formation control protocols are proposed respectively, and the graph theory is used to prove that formation control protocols can realize system formation. Furthermore, the optimal control and cooperative control are introduced into the static and the dynamic formation control protocols, and the static cooperative optimal formation control protocol and the dynamic cooperative optimal formation control protocol are designed. Through MATLAB simulation, the static cooperative optimal control protocol and static formation control protocol are compared, and the dynamic cooperative optimal control protocol and dynamic formation control protocol are compared. By comparison, the state variables of the system can reach convergence quickly, and the system can complete formation in a short time, which verifies the effectiveness of the optimal theory and cooperative control.

High grade-gliomas are highly invasive and prone to metastasis, leading to poor survival and prognosis. Currently, we urgently need a new treatment strategy to effectively inhibit glioma. In this study, artemether and paclitaxel were used as two agents for tumour suppression. Two functional materials were synthesised and modified on the surface of the micelle as targeting molecules. The addition of two functional materials confers the ability of the micelles to effectively cross the blood-brain barrier (BBB) and then target the glioma cells. Thus, this dual-targeted delivery system allows the drug to play a better role in inhibiting tumour invasion and vasculogenic mimicry (VM) channels. In this paper, the anticancer effects of dual-targeted artemether plus paclitaxel micelles on glioma U87 cells were studied in three aspects: (I) In vitro and in vivo targeting assessment, including the role of penetrating BBB and targeting glioma; (II) In vitro regulation of invasion-associated proteins; (III) Inhibition of VM channels formation and invasion in vitro; (IV) The study of pharmacodynamics in tumour-bearing mice. These results suggest that dual-targeted artemether plus paclitaxel micelle may provide a new strategy to treat glioma via inhibiting invasive and VM channels.

Abstract Background Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal adenocarcinoma (PDAC) have not been revealed yet. Methods The expression of MOB1 and lysine demethylase 2B (KDM2B) in PDAC and adjacent normal pancreas tissues were measured. Also, the underlying mechanisms of altered MOB1 expression and its impact on PDAC biology were investigated. Results We revealed for the first time that MOB1 was decreased expression in PDAC and was a statistically significant independent predictor of poor survival, and restored expression of MOB1 suppressed the proliferation, migration and invasion of PDAC cells. Further studies demonstrated that KDM2B directly bound to the promoter region of MOB1, and suppressed the promoter activity of MOB1 and transcriptionally inhibited the MOB1 expression. Furthermore, KDM2B regulated Hippo pathway and promoted PDAC proliferation, migration and invasion via MOB1. Conclusion This study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression.

Medium-low-speed maglevs are increasingly used in the urban rail transit industry because of their advantages, such as low noise and low energy consumption. In this study, a finite element analysis of the responses of the subgrade that supports a medium-low-speed maglev structure under a dynamic maglev load is presented. First, the finite element analysis considers a low-lying structure with different elastic moduli. Then, the attenuation laws of the dynamic stress and dynamic deformation for different depth ranges of the subgrade under the rail beam are analyzed. In addition, the magnitude of the influence of the dynamic load is clarified. The results lead to a recommendation of a base bed thickness of 1.5 m, graded gravel or group A filler as the surface layer of filler, and gravel soil as the bottom layer. This study provides theoretical support for the construction design of a subgrade structure under the rail beam of a low-lying maglev line.

Tumor‐derived extracellular vesicles (EVs) and their contents are involved in the development of human malignancies. Circular RNAs (circRNAs), enriched in EVs, can regulate diverse cellular processes by acting as microRNA (miRNA) sponges or through other mechanisms. In the present study, we explored the potential roles of circRNAs in EVs in the development of pancreatic ductal adenocarcinoma (PDAC). First, plasma was obtained from patients with PDAC (n = 8) and healthy volunteers (n = 8), and EVs were isolated by the ultracentrifugation method. Nanoparticle tracking analysis and transmission electron microscopy confirmed the size and form of the isolated EVs. The circRNA expression profiles of EVs were investigated by high‐throughput whole transcriptome sequencing. We then further validated the accuracy of the circRNA sequencing data by quantitative real‐time PCR analysis using plasma samples and PC cell lines, and subsequently performed bioinformatics analysis to reveal the potential functional roles of the differentially expressed circRNAs and to construct a circRNA‐miRNA interaction network to predict the target miRNAs of these circRNAs. Our work provides novel targets for further studies concerning the pathogenesis of PDAC.

High spatial resolution hyperspectral images (HR-HSIs) have shown considerable potential in urban green infrastructure monitoring. A prevalent scheme to overcome spatial resolution limitations in HSIs is by fusing low-resolution hyperspectral images (LR-HSIs) and high-resolution multispectral images (HR-MSIs). Existing methods considering the spectral dictionary or spatial dictionary can only reflect the unilateral characteristics of the HSI and cannot completely restore full information in the latent HSI. To overcome this issue, we propose a novel HSI-MSI fusion method, named DDSSLR, which joins spatial-spectral dual-dictionary and structured sparse low-rank representation. The spectral dictionary characterizing generalized spectra and the corresponding spectral sparse coefficients are extracted from LR-HSI and HR-MSI, while sparse low-rank priors of the local structure are imposed on the spectral pixels within the same superpixel in HR-MSI. Additionally, in the spatial domain, we exploit the remaining high-frequency components to learn the spatial dictionary and use the unitary transformation to factorize the spatial sparse coefficient into the sparse low-rank matrix in subspace, establishing the relationship between low-rank and sparse. We formulate the two fusion models as variational optimization problems, which are effectively solved by the alternating direction methods of multipliers (ADMM). Experiments on three HSI datasets show that DDSSLR achieves state-of-the-art performance.

Background: A pink color change occasionally found by us under magnifying endoscopy with narrow-band imaging (ME-NBI) may be a special feature of early gastric cancer (EGC), and was designated the “pink pattern”. The purposes of this study were to determine the relationship between the pink pattern and the cytopathological changes in gastric cancer cells and whether the pink pattern is useful for the diagnosis of EGC.Methods: The color features of ME-NBI images and pathological images of cancerous gastric mucosal surfaces were extracted and quantified. The cosine similarity was calculated to evaluate the correlation between the pink pattern and the nucleus-to-cytoplasm ratio of cancerous epithelial cells. Two diagnostic tests were performed by 12 endoscopists using stored ME-NBI images of 185 gastric lesions to investigate the diagnostic efficacy of the pink pattern for EGC. The diagnostic values, such as the area under the curve (AUC), the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of test 1 and test 2 were compared.Results: The cosine similarity between the color values of ME-NBI images and pathological images of 20 lesions was at least 0.744. The median AUC, accuracy, sensitivity, specificity, PPV, and NPV of test 2 were significantly better than those of test 1 for all endoscopists and for the junior and experienced groups.Conclusions: The pink pattern observed in ME-NBI images correlated strongly with the change in the nucleus-to-cytoplasm ratio of gastric epithelial cells, and could be considered a useful marker for the diagnosis of differentiated EGC.

In this paper, the distributed optimal control method is used to study the cooperative formation of heterogeneous multi-agents in the air–ground environment. The considered system consists of an unmanned aerial vehicle (UAV) and an unmanned ground vehicle (UGV). The optimal control theory is introduced into the formation control protocol, the distributed optimal formation control protocol is designed, and the stability is verified by graph theory. Furthermore, the cooperative optimal formation control protocol is designed, and the stability is analyzed using a block Kronecker product and matrix transformation theory. Through the comparison of simulation results, the introduction of optimal control theory shortens the formation time of the system and accelerates the convergence speed of the system.

Radioresistance is one of the main reasons causing unsatisfactory curative effects of ionizing radiation (IR) against colorectal cancer (CRC). However, its underlying mechanisms remain unclear yet. In the present study, we applied a genome-scale CRISPR knockout screen in combination of NGS sequencing upon CRC cell lines to explore regulatory factors involved radioresistance of CRC, and 3 candidate genes were identified. Cytotoxicity of IR was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and apoptosis assay, and microRNA-5197-5p (miR-5197) was found to significantly enhance the cytotoxicity of IR to CRC cells. By further mechanistic investigation, we demonstrated that miR-5197 directly targeted CDK6 and inhibited its expression in RKO cells, which induced cell cycle arrest at G1/S phase and inhibited cell division, thereby radiosensitivity was enhanced by miR-5197. Our findings revealed that miR-5197 might be a critical factor regulating CRC cell radiosensitivity and provided novel insights into the development of therapeutic strategies for CRC patients who are resistant to IR.

The development and innovation of veterinary drug residue analysis and detection technology is an important research content of animal-derived food safety monitoring. As an important part of systems biology, metabolomics research and its detection technology also play an indispensable role in the field of animal-derived food safety. Based on the current research results of metabolomics technology in the field of veterinary drug residue detection, the conceptual, principles and classification of metabolomics are illustrated. Taking the detection of two types of veterinary drug residues, such as clenbuterol and steroids, the current application status of the commonly used detection techniques of metabolomics contains liquid chromatography-tandem mass spectrometry (LC-MS) or gas chromatography-tandem mass spectrometry (GC-MS) on the detection of animal's blood and urine samples. The problems of untargeted metabolomics and targeted metabolomics with low precision and throughput are analyzed. The limitations of metabolomics technology over-reliance on large instrumentation and professional databases have also been offered. Further, metabolomics technology is proposed, which should be based on sample characteristics and detection purposes in the application of veterinary drug residue detection. The multi-technology platform (liquid chromatography electrospray time-of-flight mass spectrometry, ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry), multi-analysis platform (principal component analysis, partial least squares discrimination analysis) and multi-omics (genomics, transcriptomics, and proteomics) technology are used together to improve the applicability and applicational range of metabolomics technology in the field of veterinary drug residue detection. It provides new research directions for veterinary drug residue analysis and testing technology.

Inspection robots are widely used in the field of smart grid monitoring in substations, and partial discharge (PD) is an important sign of the insulation state of equipment. PD direction of arrival (DOA) algorithms using conventional beam forming and time difference of arrival (TDOA) require large-scale antenna arrays and high computational complexity, making them difficult to implement on inspection robots. To address this problem, a novel directional multiple signal classification (Dir-MUSIC) algorithm for PD direction finding based on signal strength is proposed, and a miniaturized directional spiral antenna circular array is designed in this paper. First, the Dir-MUSIC algorithm is derived based on the array manifold characteristics. This method uses strength intensity information rather than the TDOA information, which could reduce the computational difficulty and the requirement of array size. Second, the effects of signal-to-noise ratio (SNR) and array manifold error on the performance of the algorithm are discussed through simulations in detail. Then, according to the positioning requirements, the antenna array and its arrangement are developed and optimized. Simulation results suggested that the algorithm has reliable direction-finding performance in the form of six elements. Finally, the effectiveness of the algorithm is tested by using the designed spiral circular array in real scenarios. The experimental results show that the PD direction-finding error is 3.39°, which meets the need for partial discharge DOA estimation using inspection robots in substations.

Recent studies demonstrated that pyroptosis plays a crucial role in shaping the tumor-immune microenvironment. However, the influence of pyroptosis on lower-grade glioma regarding immunotherapy and targeted therapy is still unknown. This study analyzed the variations of 33 pyroptosis-related genes in lower-grade glioma and normal tissues. Our study found considerable genetic and expression alterations in heterogeneity among lower-grade gliomas and normal brain tissues. There are two pyroptosis phenotypes in lower-grade glioma, and they exhibited differences in cell infiltration characteristics and clinical characters. Then, a PyroScore model using the lasso-cox method was constructed to measure the level of pyroptosis in each patient. PyroScore can refine the lower-grade glioma patients with a stratified prognosis and a distinct tumor immune microenvironment. Pyscore may also be an effective factor in predicting potential therapeutic benefits. In silico analysis showed that patients with a lower PyroScore are expected to be more sensitive to targeted therapy and immunotherapy. These findings may enhance our understanding of pyroptosis in lower-grade glioma and might help optimize risk stratification for the survival and personalized management of lower-grade glioma patients.

Aimed at the serious mismatch between the synthetic seismogram and the real data of the Sinian Dengying Formation and the Lower Cambrian Qiongzhusi Formation in the GS1 well area, Sichuan Basin, four aspects of internal multiples identification and suppression were studied. Firstly, a forward modeling method of internal multiple based on reflectivity method was developed. Through eight means such as post-stack and pre-stack forward modeling of internal multiple, and combined with VSP data, it was demonstrated that well-seismic mismatching in this area is mainly caused by the internal multiples. Secondly, the simulation results of internal multiple forward modeling using the stripping method combined with the internal multiple periodicity analysis showed that four groups of overburden layers with velocity inversion were the main sources of the internal multiples. Thirdly, by identifying internal multiples accurately and using suppression technology based on pattern recognition, an effective and replicable suppression scheme suitable for these formations was established, overcoming the difficulty of the small speed difference between internal multiple and primary reflection wave which makes the current methods ineffective. Fourthly, an evaluation index of internal multiple intensity was proposed, and the internal multiple intensity distribution diagram of the fourth member of Dengying Formation (Deng-4 Member) in Gaoshiti-Moxi area was compiled. This scheme greatly improved the well-seismic match, and the strata sedimentary features are clearer on the new seismic profiles with higher lateral resolution, with which smaller faults and geological anomalies can be identified and a series of the bead reflections in the Dengying Formation are first discovered. The coincidence rate of reservoir prediction based on seismic waveform classification was increased from 60% to 90%, and that of hydrocarbon detection based on dual phase medium theory was increased from 70% to 100%. Key words: internal multiple, reflectivity method forward modeling, well-seismic match, velocity inversion, seismic waveform classification, hydrocarbon detection, Sichuan Basin, Sinian Dengying Formation

Objective: Endoscopic resection (ER) is more difficult and has a higher rate of complications, such as perforation and bleeding. The aim of this study was to evaluate the safety and feasibility of a bipolar polypectomy snare for ER.Methods: Initial ER procedures in live pigs were carried out. Then, a human feasibility study was performed in patients with colorectal polyps. Finally, the finite element method was used to evaluate the safety and effectiveness of the new bipolar snare.Results: In the live animal model, there were no significant differences in wound size and cutting time between monopolar and bipolar groups. The histological results (histological scores) of the two groups in porcine experiments were almost the same except that the incision flatness of bipolar group was better than that of the monopolar group. Incidence of bleeding and perforation was similar between the two groups in pigs' and patients' study. At last, the finite element model showed that the vertical thermal damage depth produced by bipolar snare system was approximately 71–76% of that produced by monopolar snare system at the same power.Conclusions: The novel bipolar snare is feasible in patients with colorectal polyps and can be an alternative choice for ERs.

In this study, a new block-type rail bearing beam is presented, which consists of a cast-in-place base and prefabricated blocks. The finite element analysis is conducted to assess the proposed new rail bearing beam structure. The performed finite element method (FEM) simulation focused on the dynamic stress at the bottom of the rail bearing beam and structural internal force and deformation under the case of train loading, etc. Besides, the relationship between first-order natural frequency and activation frequency in the new support rail beam structure is analyzed and the beneficial effects on the internode connection structure are quantified. The results show that the increase in driving speed has the most significant effect on the vertical acceleration of the structure, and the self-vibration frequency of the structure is relatively large, which means the structure is safe. Since previous research seldom focuses on this block-type rail bearing beam, this study lays a valuable foundation for the construction of a rail bearing beam for the mid-low-speed maglev train.

Very few studies have focused on diatomaceous earth slopes along high-speed railways, and the special properties of diatomaceous earth under alternating dry and wet conditions are unknown. This paper studies diatomaceous earth in the Shengzhou area, through which the newly built Hangzhou–Taizhou high-speed railway passes, and the basic physical and hydraulic properties of diatomaceous earth are analyzed by indoor test methods. A convenient, efficient, and controllable high-speed railway slope artificial rainfall simulation system is designed, and in situ comprehensive monitoring and fissure observation are performed on site to analyze the changes in various diatomaceous soil slope parameters under rainfall infiltration, and to explore the cracking mechanisms of diatomaceous earth under alternating dry and wet conditions. The results indicate extremely poor hydrophysical properties of diatomaceous earth in the Shengzhou area; the disintegration resistance index values of natural diatomaceous earth samples subjected to dry and wet cycles are 1.8–5.6%, and the disintegration is strong. Comprehensive indoor tests and water content monitoring show that natural diatomaceous earth has no obvious influence when it contacts water, but it disintegrates and cracks under alternating dry and wet conditions. The horizontal displacement of both slope types mainly occurs within 0.75–2.75 m of the surface layer, indicating shallow surface sliding; after testing, natural slope crack widths of diatomaceous earth reach 10–25 mm, and their depths reach 40–60 cm. To guarantee safety during high-speed railway engineering construction, implementing proper protection for diatomaceous earth slopes is recommended.

This study proposes a new waterproof sealing layer to reduce the impact of water on subgrade beds. The proposed waterproof sealing layer is composed of a polyurethane adhesive (PA) mixture, which aims to control interlaminar deformation and prevent seepage. A variety of laboratory tests were first performed to analyze the attenuation characteristics and mechanical properties of various polyurethane polymer (PP)-improved gravel mixtures under thermohydraulic coupling effects. In addition, a waterproof performance model test of the PP-improved gravel layer was conducted to investigate its waterproof and drainage performance and hydraulic damage mechanism. Finally, the feasibility and effectiveness of the surface structure of the waterproof drainage subgrade bed containing the PA mixture was tested in combination with the treatment project of the Ciyaowan station of the Baoshen heavy-haul railway. According to the experimental and model results, (1) the waterproof layer containing the polyurethane mixture exhibited satisfactory stiffness, elasticity and flexibility. The waterproof layer containing the polyurethane mixture also controlled the deformation between layers, and its mechanical properties remained stable. (2) The waterproof layer with the dense polyurethane mixture performed well in terms of the waterproof aspect, and no infiltration occurred under cyclic load (3). Long-term field monitoring revealed that the effect of the implementation of a PP-improved gravel layer to treat mud pumping was remarkable. The settlement of the PP-improved gravel layer only reached 13.21 mm, and the settlement remained stable in the later stage.

Abstract Background Gut microbiota plays an important role in many metabolic diseases such as diabetes and atherosclerosis. Apolipoprotein E (apoE) knock-out (KO) mice are frequently used for the study of hyperlipidemia and atherosclerosis. However, it is unknown whether apoE KO mice have altered gut microbiota when challenged with a Western diet. Methods In the current study, we assessed the gut microbiota profiling of apoE KO mice and compared with wild-type mice fed either a normal chow or Western diet for 12 weeks using 16S pyrosequencing. Results On a western diet, the gut microbiota diversity was significantly decreased in apoE KO mice compared with wild type (WT) mice. Firmicutes and Erysipelotrichaceae were significantly increased in WT mice but Erysipelotrichaceae was unchanged in apoE KO mice on a Western diet. The weighted UniFrac principal coordinate analysis exhibited clear separation between WT and apoE KO mice on the first vector (58.6%) with significant changes of two dominant phyla (Bacteroidetes and Firmicutes) and seven dominant families (Porphyromonadaceae, Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, Helicobacteraceae, Erysipelotrichaceae and Veillonellaceae). Lachnospiraceae was significantly enriched in apoE KO mice on a Western diet. In addition, Lachnospiraceae and Ruminococcaceae were positively correlated with relative atherosclerosis lesion size in apoE KO. Conclusions Collectively, our study showed that there are marked changes in the gut microbiota of apoE KO mice, particularly challenged with a Western diet and these alterations may be possibly associated with atherosclerosis.

To reveal the effect of Mg treatment on the microstructure evolution behavior in the actual steel welding process, the microstructure and properties of Al-deoxidized high-strength ship plate steel with Mg addition were analyzed after double-side submerged arc welding. It was found that the Al–Mg–O + MnS inclusion formed under 26 ppm Mg treatment could promote acicular ferrite (AF) nucleation in the coarse-grained heat-affected zone (CGHAZ) and inhibit the formation of widmanstätten ferrite and coarse grain boundary ferrite. In the fine-grained heat-affected zone (FGHAZ) and intercritical heat-affected zone (ICHAZ), polygonal ferrite and pearlite were dominant. Al–Mg–O+MnS cannot play a role in inducing AF, but the grain size of ferrite was refined by Mg addition. The impact toughness in HAZ of the Mg-added steel was higher than that of Mg-free steel. With the heat-input rising from 29.55 to 44.11 kJ/cm, it remained relatively stable in Mg-treated steel. From the fusion line to the base metal, the micro-hardness of the fusion zone, CGHAZ, ICHAZ and FGHAZ decreased to some extent after Mg addition, which means the cold cracking tendency in the welding weak zone could be reduced. Finally, the mechanisms of Mg-containing inclusion-induced AF were also systematically discussed.

As part of concepts for chemical energy storage of excess chemical energy produced from renewable sources, we investigated the performance of CuO/ZnO catalysts supported on mesoporous carbon to convert CO2 hydrogenation to methanol. In this work, mesoporous carbon was used as the catalyst support for CuO-ZnO catalysts. Four catalysts with different precipitated precursors were synthesized and analyzed by N2-physisorption, X-ray diffraction (XRD), thermogravimetric analysis (TG-DTG), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results show that catalyst CZ-in situ had the highest turnover frequency (TOF) (2.8 × 10−3 s−1) and methanol production rate (0.8 mmol g−1·h−1). The catalysts for co-precipitation of copper and zinc on carbon precursors are more active. Cu/ZnO domains that are accessible to the reactant gas are another reason for the catalysts being active. The Cu-ZnO interface is crucial to methanol catalyst activity.

A new process of extracting titanium from vanadium–titanium magnetite (VTM) in the Panxi area in Sichuan, China is introduced in this work. Various experiments, including reduction–magnetic separation, leaching and hydrolyzing experiments, are carried out. The results show that the optimum conditions for leaching experiments are an acid/slag ratio of 4:1, a leaching temperature of 60 °C, a leaching time of 80 min, and a liquid/solid ratio of 3.2:1. The leaching rate of titanium in Ti-bearing slag is 92.41%. The optimum conditions for hydrolyzing experiments are an H+ concentration of 0.75 g·L−1, hydrolyzing temperature of 100 °C, and hydrolyzing time of 180 min, and the hydrolyzing rate of titanium in acid leaching liquor is 96.80%. After the leaching and hydrolyzing experiments, the recovery rate of titanium from the Ti-bearing slag is 89.45%.

The Al2O3-SiO2, La2O3-Al2O3, and La2O3-SiO2 binary phase diagrams were estimated by Redlich−Kister expression. La4.67Si3O13 (=La4.67(SiO4)3O) was introduced to improve the existing phase diagrams. The Al2O3-SiO2-La2O3 ternary phase diagram extrapolated by Kohler method was optimized. Then, the liquidus of Al2O3-SiO2-La2O3 system at 1600 °C was compared with Al2O3-SiO2-RE2O3 (RE = Rare Earth Elements) systems and experimental results in other literature. The high temperature experiments were conducted in the tube furnace at 1500 °C. Then the field emission scanning electron microscope (FE-SEM), energy dispersive spectrometer (EDS), and X-ray diffraction (XRD) were employed to verify the calculated liquid region and precipitates phase at 1500 °C. Moreover, the liquidus of binary systems were compared with FactSage results and experiments. The optimized ternary phase diagram shows the relatively reliable region of liquid phase, and it is significant to the seal glass of solid oxide fuel cells and other fields being related to RE containing silicates.

To solve the nozzle clogging issue in the continuous casting process of 253MA steel, a method of modifying solid inclusions to liquid phases is proposed. The CALPHAD technique was employed to predict the liquid region of the Al2O3-SiO2-Ce2O3 system. Then a thermodynamic package based on the extracted data during the phase diagram optimization process was developed. This package was then used to compute the appropriate aluminum addition, which was 0.01% in 253MA steel. The Si-Al alloy was chosen as the deoxidant according to the thermodynamic analysis. The solid inclusions were ultimately modified to liquid phases at 1500 °C when cerium was added through the equilibrium experiments in a MoSi2 tube furnace.

The binary structure of the floodplain in the reaches of the Yangtze River is obvious and has unique hydrogeological features. In this paper, the hydrogeological survey of the floodplain area is carried out. It is found that the permeability coefficient of the floodplain area is gradually increasing from top to down, and is larger than that of the similar layer in other areas. The horizontal and vertical permeability coefficients are not much different. This hydrological survey results of this paper provide a certain reference for similar dewatering projects in the floodplain area of the lower reaches of the Yangtze River.