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Abstract Solid stress, originating from rigid and elastic components of extracellular matrix and cells, is a typical physical hallmark of tumors. Mounting evidence indicates that elevated solid stress drives metastasis and affects prognosis. However, the molecular mechanism of how cancer cells sense solid stress, thereby exacerbating malignancy, remains elusive. In this study, our clinical data suggest that elevated stress in metastatic solid tumors is highly associated with the expression of cytoskeleton-associated protein 4 (CKAP4). Intriguingly, CKAP4, as a sensitive intracellular mechanosensor, responds specifically to solid stress in a subset of studied tumor micro-environmental elements through liquid–liquid phase separation. These micron-scaled CKAP4 puncta adhere tightly onto microtubules and dramatically reorchestrate their curvature and branching to enhance cell spreading, which, as a result, boosts cancer cell motility and facilitates distant metastasis in vivo. Mechanistically, the intrinsically disordered region 1 (IDR1) of CKAP4 binds to microtubules, while IDR2 governs phase separation due to the Cav1.2-dependent calcium influx, which collectively remodels microtubules. These findings reveal an unprecedented mechanism of how cancer cells sense solid stress for cancer malignancy and bridge the gap between cancer physics and cancer cell biology.

Abstract Car wheels are crucial to automobile safety, requiring a rigorous test before production. A 90° impact test simulates the frontal impact and its influences on the wheel structure, replicating dynamic driving conditions. A novel modelling approach is illustrated for the 90° impact test simulation and investigates the feasibility of excluding the tyre. Firstly, the test performs and validates five impact simulations, with the maximum deformation error being 7.04%. Subsequently, with additional tests, the effectiveness of the modelling approach is evaluated. Lastly, the effect of tyres has been analysed from an energy perspective. The results indicate that the tyre significantly influences the simulation results and should be included in the finite element (FE) model, which differs from the 13° impact test.

Abstract The integration of multiple functionalities into a single, planar, ultra-compact metasurface has presented significant opportunities for enhancing capacity and performance within compact 5G/6G communication systems. Recent advances in multifunctional metasurfaces have unveiled comprehensive wavefront manipulations utilizing phase, polarization transmission/reflection, and coding apertures. Despite these developments, there remains a critical need for multifunctional metasurfaces with expanded channel capabilities, including multiple operational frequencies, minimal crosstalk, and high-efficiency computable array factors. This study introduces a multifunctional metasurface that integrates phase- and amplitude simultaneous coding meta-atoms at dual frequencies. By altering the polarization of electromagnetic (EM) waves, it is possible to reshape the wave-fronts of reflected waves at these frequencies. The coding metasurface proficiently manipulates both x and y linearly polarized waves through phase and amplitude coding at dual frequencies, thereby enabling distinct functionalities such as anomalous reflection, reflection imaging, and vortex wave beam generation. Both theoretical analysis and full-wave simulation confirm the anticipated functionalities of the designed devices, paving the way for advancements in integrated communication systems with diverse functionalities.

Abstract Background The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. Methods we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. Findings We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. Interpretation The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

To address the safety and efficient driving issues of human–machine shared control vehicles (HSCVs) in future complex traffic environments, this paper proposes a game theory-based interactive control method between HSCVs and surrounding autonomous vehicles (SVs) and involves considering different driving behaviors. In HSCV, a comprehensive driver model integrating steering control and speed control is designed based on the brain emotional learning circuit model (BELCM), and the control authority between the driver and the automation system is dynamically allocated through the evaluation of the driving safety field. Factors such as driving safety and travel efficiency that reflect personalized driving style are considered for modeling the uncertain behavior of SVs. In the interaction between HSCVs and SVs, a method based on game theory and distributed model predictive control (DMPC) that considers the uncertainty of SVs’ driving behavior is established and is finally integrated into a multi-objective constraint problem. The driver control input in an HSCV will also be introduced into the solution process. To demonstrate the feasibility of the proposed method, two test scenarios considering the driving characteristics of different SVs are established. The test results show that automation control systems can promptly stop the human driver’s dangerous operations in an HSCV and safely interact with multiple AVs with different driving characteristics.

Because of the fast deterioration speed of the surface function of conventional asphalt pavement, thin overlayer with many advantages has been applied to the pavement surface. However, due to problems such as insufficient stripping resistance and cracking resistance, the performance of the thin overlayer needs to be further improved. To achieve this target, basalt fiber was introduced into two types of thin overlayer asphalt mixtures (Open graded friction course, OGFC-5, and Stone matrix asphalt mixture, SMA-5). The wheel tracking test and uniaxial penetration test for high temperature deformation resistance, low temperature bending beam test and indirect tensile asphalt (IDEAL) cracking test for cracking resistance, cantabro test for stripping resistance, and friction coefficient test for skid resistance were conducted to evaluate various performance of thin overlayer asphalt mixtures, along with the dynamic modulus test for dynamic mechanical response. The results showed that adding basalt fiber could enhance the high temperature deformation resistance, low temperature cracking resistance, intermediate temperature cracking resistance and stripping resistance of the thin overlayer, while having no significant impact on skid resistance. Furthermore, adding basalt fiber could increase the modulus in the high temperature region and decrease the modulus in the low temperature region of the thin overlayer asphalt mixtures, indicating thin overlayer with basalt fiber presenting superior both high temperature and low temperature performance. In addition, the evaluation indexes of SLT and SHT proposed from dynamic modulus test exhibited good consistency with the results of the performance tests.

The X90 pipeline steel pipe is expected to become the standard steel in future pipeline construction due to its high transmission efficiency and lower cost. However, little study has been conducted on corrosion on-line monitoring of X90 steel. To investigate the pitting development of X90 steel, a combined electrochemical device and acoustic emission (AE) system was set up in this work. The results reveal that the pitting process can be divided into three stages: activation response and passive film rupture, and corrosion pit propagation, and pitting reaction. In addition, the corrosion rate of metal is quite high during the activation reaction and passivation film rupture stage, and the characteristic parameters of the AE signal are very large. In the frequency domain, the frequency range is mostly centered between 100 and 200 kHz, with a peak frequency of about 150 kHz. The corrosion pit propagation stage is the transition stage from metal oxidation to metal pitting reaction. The activity of the signal is low, and the characteristic signal is diminished, and the frequency domain characteristics are comparable to the preceding stage. The signal activity rises, the total signal intensity increases, and several signals exceeding 55 dB arise during the pitting response stage.

Background & Aims: Exploiting key regulators responsible for hepatocarcinogenesis is of great importance for the prevention and treatment of hepatocellular carcinoma (HCC). However, the key players contributing to hepatocarcinogenesis remain poorly understood. We explored the molecular mechanisms underlying the carcinogenesis and progression of HCC for the development of potential new therapeutic targets. Methods: The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and Genotype-Tissue Expression (GTEx) databases were used to identify genes with enhanced expression in the liver associated with HCC progression. A murine liver-specific Ftcd knockout (Ftcd-LKO) model was generated to investigate the role of formimidoyltransferase cyclodeaminase (FTCD) in HCC. Multi-omics analysis of transcriptomics, metabolomics, and proteomics data were applied to further analyse the molecular effects of FTCD expression on hepatocarcinogenesis. Functional and biochemical studies were performed to determine the significance of loss of FTCD expression and the therapeutic potential of Akt inhibitors in FTCD-deficient cancer cells. Results: FTCD is highly expressed in the liver but significantly downregulated in HCC. Patients with HCC and low levels of FTCD exhibited worse prognosis, and patients with liver cirrhosis and low FTCD levels exhibited a notable higher probability of developing HCC. Hepatocyte-specific knockout of FTCD promoted both chronic diethylnitrosamine-induced and spontaneous hepatocarcinogenesis in mice. Multi-omics analysis showed that loss of FTCD affected fatty acid and cholesterol metabolism in hepatocarcinogenesis. Mechanistically, loss of FTCD upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element–binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis. Conclusions: Taken together, we identified a FTCD-regulated lipid metabolic mechanism involving PPARγ and SREBP2 signaling in hepatocarcinogenesis and provide a rationale for therapeutically targeting of HCC driven by downregulation of FTCD. Impact and implications: Exploiting key molecules responsible for hepatocarcinogenesis is significant for the prevention and treatment of HCC. Herein, we identified formimidoyltransferase cyclodeaminase (FTCD) as the top enhanced gene, which could serve as a predictive and prognostic marker for patients with HCC. We generated and characterised the first Ftcd liver-specific knockout murine model. We found loss of FTCD expression upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element–binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis, and provided a rationale for therapeutic targeting of HCC driven by downregulation of FTCD.

PurposeTo explore the predictive value of multiple immune-inflammatory biomarkers including serum VEGFA and systemic immune-inflammation index (SII) in HER2-negative advanced gastric cancer (AGC) and establish nomograms for predicting the first-line chemotherapeutic efficacy, progression-free survival (PFS) and overall survival (OS) of patients with this fatal disease.MethodsFrom November 2017 to April 2022, 102 and 34 patients with a diagnosis of HER2-negative AGC at the First Affiliated Hospital of Bengbu Medical College were enrolled as development and validation cohorts, respectively. Univariate and multivariate analyses were performed to evaluate the clinical value of the candidate indicators. The variables were screened using LASSO regression analysis. Predictive models were developed using significant predictors and are displayed as nomograms.ResultsBaseline VEGFA expression was significantly higher in HER2-negative AGC patients than in nonneoplastic patients and was associated with malignant serous effusion and therapeutic efficacy (all p

Abstract Background This study analyzed the safety and efficacy of Enterprise 2 stent-assisted coil embolization for wide-necked intracranial aneurysms by examining stent-vessel apposition, operative complications, embolization outcomes, and clinical outcomes. Methods We retrospectively reviewed the medical records of patients with wide-necked intracranial aneurysms who underwent Enterprise 2 stent-assisted coiling in our hospital from November 2018 to October 2019. Intraoperative VasoCT was performed immediately after stent release in a continuous cohort of patients to observe stent-vessel apposition. Patient demographic, clinical, and imaging data were recorded and analyzed. Results A total of 106 wide-necked aneurysms in 106 patients were treated. Stent release was successful in all patients. Twenty-one patients were enrolled consecutively for VasoCT scanning, and incomplete stent apposition was observed in 5 (23.8%). Perioperative complications occurred in 10 patients (9.4%): cerebral infarction in 6, intraoperative coil prolapse in 1, puncture site pseudoaneurysm in 1, deep vein thrombosis at multiple sites in 1, and transient brainstem mass effect in 1. Among the 95 aneurysms with angiographic follow-up, embolization was satisfactory (Raymond–Roy classifications I and II) in 89 (93.7%). Hyperlipidemia was an independent risk factor for incomplete aneurysm occlusion. At the last clinical follow-up, seven patients had a poor clinical outcome (modified Rankin Scale score ≥ 3). Independent risk factors for poor outcomes were preoperative subarachnoid hemorrhage at presentation and cerebral infarction. Conclusion Enterprise 2 stent-assisted coiling for treatment of wide-necked intracranial aneurysms showed good safety and efficacy; however, incomplete stent apposition can still occur in vessels with a large curvature. Preoperative subarachnoid hemorrhage at presentation and cerebral infarction are the main reasons for poor clinical outcomes after stent-assisted coil embolization.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Abstract Background This paper aimed to review the databases on non-displaced femoral neck fractures in elderly patients. We also discussed the surgical and non-surgical treatments and selection of implants. Methods Reviewed was the literature on non-displaced femoral neck fractures in elderly patients. Four major medical databases and a combination of the search terms of “femoral neck fractures”, “nondisplaced”, “undisplaced”, “non-displaced”, “un-displaced”, “aged”, “the elderly”, and “geriatric” were used to search the literature relevant to the topic of the review. Results Patients who were unable to tolerate the operation and anesthesia could be treated conservatively. Otherwise, surgical treatment was a better choice. Specific surgical strategies and implant selection were important for the patient’s functional recovery. Conclusions The non-displaced femoral neck fractures are relatively stable but carry a risk of secondary displacement. Surgical treatments may be a better option because the implants provide additional stability and allow early exercise and ambulation. Hemiarthroplasty is also an alternative for old patients with higher risks of displacement and avascular necrosis of the femoral head.

Abstract The echinoderm microtubule associated protein‐like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non‐small‐cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)‐ALK rearrangement is extremely rare. The co‐occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1‐ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions after she acquired osimertinib resistance. Furthermore, we summarize 22 published cases of patients with lung adenocarcinoma with concurrent EGFR mutation and ALK rearrangement, including details of clinical characteristics, natural history, and pertinent therapy of this uncommon tumor subtype. This literature review shows that EGFR inhibition was an indispensable aspect of the treatment of patients with EGFR/ALK co‐alterations in the pre‐alectinib era and that ALK inhibition with crizotinib did not show more eye‐catching therapeutic results. Considering the effectiveness achieved by alectinib, this case study provides a new perspective for the treatment of lung cancer brain metastasis patients with concurrent EGFR/ALK mutations.

Climate change has caused an increase in the frequency of flood events. Rapid and accurate flood mapping is essential for disaster monitoring and risk assessment. The normalized difference flood index (NDFI) is a change detection method with the characteristics of efficient processing and less manual intervention, which can quickly obtain flood information. However, the NDFI method would misclassify some permanent water bodies in lakes and rivers into floods. We presented a framework by combining NDFI calculated from synthetic aperture radar images and a summer permanent water bodies (SPWB) exclusion layer derived from optical remote sensing surface reflectance data, abbreviated as NDFI-SPWB. This framework was further verified by the flood event in the Yangtze river basin in July 2020. Results show that the NDFI-SPWB framework can increase the user accuracy by approximately 10% and the Kappa coefficient by approximately 0.08 compared with the original NDFI method, which verifies the feasibility and effectiveness of the proposed framework.

Cytokines play vital roles in the pathogenesis of inflammatory bowel disease. IL17B is protective in the development of colitis. However, how IL17B regulates intestinal inflammation and what cells are regulated by IL17B is still unknown. Here, we aimed to illustrate the IL17B dependent cellular and molecular changes in colon tissue in a mouse colitis model. The results showed that IL17B expression in colon tissues was elevated in inflamed tissues than non-inflamed tissues of IBD patients. Wild type (WT) and Il17b deficient (Il17b-/-) mice were given 2.5% dextran sodium sulfate (DSS) water, and in some case, Il17b-/- mice were treated with recombinant mouse IL17B. IL17B deficiency resulted in severe DSS-induced colitis with exaggerated weight loss, shorter colon length, and elevated proinflammatory cytokines in colon. Reconstitution of Il17b-/- mice with recombinant IL17B alleviated the severity of DSS-induced colitis. Single cell transcriptional analyses of CD45+ immune cells in colonic lamina propria revealed that loss of IL17B resulted in an increased neutrophil infiltration and enhanced inflammatory cytokines in intestinal macrophages in colitis, which were confirmed by real-time PCR and flow cytometry. IL17B treatment also inhibited lipopolysaccharide-induced inflammation in bone marrow-derived macrophages and mice. IL17B inhibits colitis by regulating colonic myeloid cell response. It might represent a novel potential therapeutic approach to treat the colitis.

Summary: Membraneless condensates, such as stress granules (SGs) and processing bodies (P-bodies), have attracted wide attention due to their unique feature of rapid response to stress without first requiring nuclear feedback. In this study, we identify diaphanous-related formin 3 (DIAPH3), an actin nucleator, as a scaffold protein to initiate liquid-liquid phase separation (LLPS) and form abundant cytosolic phase-separated DIAPH3 granules (D-granules) in mammalian cells such as HeLa, HEK293, and fibroblasts under various stress conditions. Neither mRNAs nor known stress-associated condensate markers, such as G3BP1, G3BP2, and TIA1 for SGs and DCP1A for P-bodies, are detected in D-granules. Using overexpression and knockout of DIAPH3, pharmacological interventions, and optogenetics, we further demonstrate that stress-induced D-granules spatially sequester DIAPH3 within the condensation to inhibit the assembly of actin filaments in filopodia. This study reveals that D-granules formed by LLPS act as a regulatory hub for actin cytoskeletal remodeling in response to stress.

Summary: Background: Identification of tumor dependencies is important for developing therapeutic strategies for liver cancer. Methods: A genome-wide CRISPR screen was performed for finding critical vulnerabilities in liver cancer cells. Compounds screen, RNA sequencing, and human phospho-receptor tyrosine kinase arrays were applied to explore mechanisms and search for synergistic drugs. Findings: We identified mitochondrial translation-related genes associated with proliferation for liver cancer cells. Tigecycline induced deficiency of respiratory chain by disturbing mitochondrial translation process and showed therapeutic potential in liver cancer. For liver cancer cells extremely insensitive to tigecycline, a compounds screen was applied to identify MEK inhibitors as synergistic drugs to tigecycline-insensitive liver cancer cells. Mechanistically, sustained activation of EGFR-ERK1/2-MYC cascade conferred the insensitivity to tigecycline, which was mediated by enhanced secretion of EREG and AREG. Moreover, glycolytic enzymes, such as HK2 and PKM2 were upregulated to stimulate glycolysisin a MYC-dependent manner. Tigecycline induced respiratory chain deficiency in combination with cutting off EGFR-ERK1/2-MYC cascade by MEK inhibitors or EGFR inhibitors, resulting in decrease of both oxidative phosphorylation and glycolysis in liver cancer cells. Interpretation: Our study proved that blocking EGFR-ERK1/2-MYC cascade combined with tigecycline could be a potential therapeutic strategy for liver cancer. Funding: This work was funded by grants from the National Natural Science Foundation of China (82073039, 82222047, 81920108025), Program of Shanghai Academic/Technology Research Leader (22XD1423100), Shanghai Municipal Science and Technology Project (20JC1411100), 111 Project (B21024), Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212700, SHSMU-ZDCX20210802) and Shanghai Jiao Tong University School of Medicine (YG2019GD01).

BackgroundVertebrobasilar dissecting aneurysms (VBDAs) with an intramural hematoma (IMH) usually cause symptoms because of mass effect and grow in size over time. Clinical outcomes are generally poor.ObjectiveThis study aimed to examine outcomes of reconstructive endovascular treatment (EVT) in patients with VBDAs with IMH. Safety and effectiveness were compared between flow diverters (FDs) and conventional stents.MethodsWe retrospectively analyzed the clinical and radiological data of 36 VBDAs with IMH in 36 patients who underwent EVT with either FDs or conventional stents from January 2012 to December 2020 at our institution.ResultsAmong the 36 study patients, 20 were treated with FDs and 16 with conventional stents. Incidence of procedure-related complications did not significantly differ between the two stents. IMH growth occurred after EVT in a significantly higher proportion of conventional stent group aneurysms (zero vs. 31.3% [5/16]; p = 0.012). Among the five aneurysms with IMHs that grew, all recurred. Change in IMH size after EVT was significantly lower in the FD group (−2.7 vs. +8.1%, p = 0.036). However, after the recurrent aneurysms were removed from the conventional stent group, change in IMH size did not significantly differ between the two groups (−2.7 vs. +1.0%, p = 0.332). The proportion of patients who experienced an improvement in mRS score after EVT was significantly higher in the FD group (60 vs. 25%, p = 0.036).ConclusionIMHs in VBDAs stop growing after successful reconstructive EVT. Although both FD and conventional stent treatment are effective, FD treatment may be superior based on clinical outcomes and effect on IMH size.

Circular RNAs (circRNA) is a class of non-coding RNAs that can regulate gene translation and function. Here the authors show that a circRNA, circNDUFB2, is downregulated in non-small cell lung cancer tissues, and likely contributes to anti-tumor immunity by regulating both degradation of oncoproteins and induction of innate immunity.

BackgroundBasilar trunk and vertebrobasilar junction (BTVBJ) aneurysms have a poor prognosis and are challenging to treat.ObjectiveThis study aimed to evaluate the efficacy of reconstructive endovascular treatment for BTVBJ aneurysms and explore a treatment selection paradigm.MethodsClinical and angiographic data from 77 patients with 80 BTVBJ aneurysms who underwent endovascular treatment with flow diverters (FDs) or conventional stent-assisted coiling between January 2016 and December 2020 were retrospectively analyzed. Aneurysm characteristics and treatment outcomes were compared between treatment groups.ResultsAmong the 77 study patients, 34 (44.2%) were treated with FDs and 43 (55.8%) with conventional stent-assisted coiling. Overall, 72.7% of patients achieved favorable clinical outcome at follow-up. The rate of procedure-related complications was 23.4%. The aneurysm occlusion rate at last follow-up did not differ between the FD and conventional stent groups (79.2% vs. 77.1%, p = 0.854). Although the occlusion rate immediately after the procedure was lower in the FD group (29.4%), incidence of progressive occlusion was significantly higher (62.5 vs. 5.7%; p < 0.001). The proportion of patients with large and giant aneurysms (≥10 mm) was significantly higher in the FD group (70.6 vs. 34.8%; p = 0.002). In patients with large or giant aneurysms, favorable clinical outcome at last follow-up was achieved in 75% of patients in the FD group but only 43.8% of patients in the conventional stent group (p = 0.046). Moreover, the complication rate was lower in the FD group, but the difference was not significant (20.8 vs. 37.5%; p = 0.247). The same analyses were performed for patients with small aneurysms (

In view of the problem of large network latency when the controller synchronized information to maintain the global network view,the latency-based SDN controller on-demand placement scheme was proposed.Firstly,the satellite subnet division method based on redundant coverage was designed according to the relative velocity of satellite and terminal.Then,the controller placement model was established by analyzing the response latency of the satellite distributed control.Finally,the controller placement problem was transformed into the soft capacitated facility location problem,and the approximation algorithm was designed to solve the model.The experimental results show that the proposed scheme can optimize network latency while meeting networking coverage demands.

Medical images are playing an important role in the medical domain. A mature medical visual question answering system can aid diagnosis, but there is no satisfactory method to solve this comprehensive problem so far. Considering that there are many different types of questions, we propose a model called CGMVQA, including classification and answer generation capabilities to turn this complex problem into multiple simple problems in this paper. We adopt data augmentation on images and tokenization on texts. We use pre-trained ResNet152 to extract image features and add three kinds of embeddings together to deal with texts. We reduce the parameters of the multi-head self-attention transformer to cut the computational cost down. We adjust the masking and output layers to change the functions of the model. This model establishes new state-of-the-art results: 0.640 of classification accuracy, 0.659 of word matching and 0.678 of semantic similarity in ImageCLEF 2019 VQA-Med data set. It suggests that the CGMVQA is effective in medical visual question answering and can better assist doctors in clinical analysis and diagnosis.

SnO2 is a promising anode material for lithium-ion batteries due to its high theoretical specific capacity and low operation voltage. However, its poor cycling performance hinders its commercial application. In order to improve the cycling stability of SnO2 electrodes, novel flower-like SnO2/TiO2 hollow spheres were prepared by facile hydrothermal method using carbon spheres as templates. Their flower-like shell and mesoporous structure highlighted a large specific surface area and excellent ion migration performance. Their TiO2 hollow sphere matrix and 2D SnO2 nano-flakes ensured good cycle stability. The electrochemical measurements indicated that novel flower-like SnO2/TiO2 hollow spheres delivered a high specific capacity, low irreversible capacity loss and superior rate performance. After 1,000 cycles at current densities of 200 mA g−1, the capacity of the flower-like SnO2/TiO2 hollow spheres was still maintained at 720 mAh g−1. Their rate capacity reached 486 mAh g−1 when the current densities gradually increase to 2,000 mA g−1.

In the original publication [...]

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

Background: Intraplaque neovascularisation (IPN) increases the vulnerability of plaques, which makes them more likely to rupture and increases the risk of vascular events. However, it is unclear whether IPN can predict future vascular events (stroke recurrence and cardiovascular events). Previous studies on IPN have focused on patients with severe stenosis but overlooked patients with mild and moderate stenosis. This study aimed to investigate whether IPN assessed by contrast-enhanced ultrasonography (CEUS) in patients with mild and moderate degrees of stenosis is associated with future vascular events. Methods: One hundred and twenty-one patients participated in this study. 76 patients who met the inclusion and exclusion criteria were included in the final dataset of the study. IPN was graded from 0 to 2 according to the extent of the microbubbles assessed using CEUS. The degree of carotid stenosis was graded as mild, moderate, or severe. We recorded future vascular events during the follow-up. Univariate and multivariate logistic regression analyses were used to evaluate risk factors for future vascular events. Results: After a follow-up period of 30 ± 6 months, 30 patients (39.5%) experienced subsequent vascular events. Compared with the ‘non-recurrent’ group, the ‘recurrent’ group showed a higher proportion of grade 2 neovascularisation ( p

Abstract Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease that comprises ulcerative colitis (UC) and Crohn’s disease (CD). IBD involves the ileum, rectum, and colon, and common clinical manifestations of IBD are diarrhea, abdominal pain, and even bloody stools. Currently, non-steroidal anti-inflammatory drugs, glucocorticoids, and immunosuppressive agents are used for the treatment of IBD, while their clinical application is severely limited due to unwanted side effects. Chinese medicine (CM) is appealing more and more attention and investigation for the treatment of IBD owing to the potent anti-inflammation pharmacological efficacy and high acceptance by patients. In recent years, novel drug delivery systems are introduced apace to encapsulate CM and many CM-derived active constituents in order to improve solubility, stability and targeting ability. In this review, advanced drug delivery systems developed in the past and present to deliver CM for the treatment of IBD are summarized and future directions are discussed.

Abstract Background Flow diverter devices are increasingly used for endovascular treatment of internal carotid artery aneurysms. Treatment of ophthalmic segment aneurysms with flow diverter devices also includes coverage of the ophthalmic artery but may result in complications. It is unclear, however, whether these devices mechanically block blood flow in the ophthalmic artery. Also unclear is the relationship between deployment of a flow diverter device and post-treatment occlusion. We studied hemodynamic changes in the ophthalmic artery after deployment of a flow diverter device to determine the relationship between those changes and post-stent occlusion of the artery. Methods We analyzed hemodynamic modifications in the ophthalmic artery in 21 patients (19 women, 2 men; mean age 53.43 ± 7.32 years) treated by a single pipeline embolization device. Patient-specific geometries were determined from three-dimensional digital subtraction angiography and the stenting process was simulated. Computational fluid dynamics technology was used to analyze the change in ophthalmic artery hemodynamics. We compared pre-treatment and post-treatment flow velocity of the ophthalmic artery. Results Among the 21 patients with aneurysms located in the ophthalmic segment, no ophthalmic artery occlusion was found during immediate or follow-up angiography. Post-stent flow velocity in the ophthalmic artery decreased from 0.35 ± 0.19 to 0.33 ± 0.20 m/s, with the difference not being statistically significant (P = 0.106). Conclusion Our results showed no significant change in ophthalmic artery blood flow after pipeline embolization device deployment. Hence, post-stent occlusion of the ophthalmic artery could not be explained by reduced blood flow. Delayed thrombosis and neointimal formation maybe the keys to ophthalmic artery occlusion and need further investigation.

Abstract Background and objective Endoscopic submucosal dissection (ESD) is a minimal invasive technology and could allow “en bloc” resection for superficial gastric tumors. The aim of this study is to evaluate the safety and feasibility of ESD for gastric ectopic pancreas (EP). Methods A total of 93 patients diagnosed with ectopic pancreas who underwent ESD between January 2011 and June 2017 were enrolled. The demographic, clinical, and endoscopic data were collected and analyzed. Results The average maximal diameter of lesions was 1.01 (range 0.4–3.0) cm with mean age of patients which was 39.75 (range 15–66) years. Overall, all of procedures en bloc was successful. The median operative time was 76.87 (range 30–160) min. A total of 12 patients experienced complications. In seven patients, bleeding occurred during the operation and was treated using hot biopsy forceps or metal clip. Five cases suffered from pneumoperitoneum which was managed well. The mean length of postoperative hospital stay was 5.7 (range 2–17) days. There was no relapse in any cases during the follow-up. Conclusion ESD appears to be a safe and feasible approach for curative treatment in gastric ectopic pancreas. Larger studies are needed to identify the role and the outcomes of ESD in another center.

Abstract Biofilm is a natural form of bacterial growth ubiquitously in environmental niches. The biofilm formation results in increased resistance to negative environmental influences including resistance to antibiotics and antimicrobial agents. Quorum sensing (QS) is cell-to-cell communication mechanism, which plays an important role in biofilm development and balances the environment when the bacteria density becomes high. Due to the prominent points of biofilms implicated in infectious disease and the spread of multi-drug resistance, it is urgent to discover new antibacterial agents that can regulate biofilm formation and development. Accumulated evidences demonstrated that natural products from plants had antimicrobial and chemo-preventive properties in modulation of biofilm formation in the last two decades. This review will summarize recent studies on the discovery of natural anti-biofilm agents from plants with clear-cut mechanisms or identified molecular addresses, as well as some herbs with unknown mechanisms or unidentified bioactive ingredients. We also focus on the progression of techniques on the extraction and identification of natural anti-biofilm substances. Besides, anti-biofilm therapeutics undergoing clinical trials are discussed. These newly discovered natural anti-biofilm agents are promising candidates which could provide novel strategies for biofilm-associated infections.

Abstract Background The combination of Radix Paeoniae Alba (RPA) and Rhizoma Atractylodis Macrocephalae (RAM) has long been used as a classic herb pair for the treatment of gynecologic and gastrointestinal diseases, but the underlying mechanisms of the herb pair remain unknown. This study aims to explore the anti-inflammatory potentials of RPA–RAM herb pair and to elucidate the underlying mechanisms. Methods The bioactive parts of RPA–RAM were extracted and screened through the inhibitory effects against nitric oxide (NO) production. The effects of optimized RPA–RAM extracts (OPAE) on inflammation-associated mediators were investigated by Western blotting, real-time quantitative PCR (RT-qPCR), Enzyme-linked immunosorbent (ELISA) and immunofluorescence staining. Results OPAE potently suppressed the productions of NO, TNF-α, IL-6 and MCP-1 in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, concentration-dependently inhibited protein level of inducible nitric oxide synthase (iNOS), dramatically downregulated mRNA expression of iNOS, TNF-α, IL-6 and MCP-1. In addition, OPAE significantly prevented phosphorylation and degradation of inhibitory kappa Bα (IκBα) and subsequently restrained the nuclear translocation of NF-κB p65. Pretreatment with OPAE also attenuated the LPS-induced phosphorylation of ERK, JNK and p38. Conclusions Our findings demonstrated that OPAE suppressed inflammatory responses in LPS-stimulated RAW 264.7 macrophages by decreasing critical molecules involved in MAPK and NF-κB pathway, suggesting that the herb pair could be a promising therapeutic candidate for inflammation-related diseases.

AZ63 sacrificial anode is widely used to protect buried metal pipelines and reinforced concrete structures and so on. The interfacial metallurgical bonding between AZ63 sacrificial anode and Q235 wiring terminal directly affects its cathodic protection performance. Therefore, microstructure and mechanical properties of interfacial between AZ63 and Q235 by solid–liquid compound casting with hot-dip galvanized and post-casting solution-aging treatment (T6) were investigated. The results indicate that hot-dip galvanizing on the surface of Q235 is beneficial to the formation of intermetallic compounds at the interface. At the same time, it can promote the metallurgical bonding of the interface between AZ63 and Q235. After T6 heat treatment, the intermetallic compound at the interface between AZ63 and galvanized Q235 was refined. The electron-probe microanalyzer (EPMA) revealed that the intermetallic compounds at the interfaces between AZ63 and galvanized Q235 were Fe2Al5 before and after T6 treatment. Push-out testing and microhardness were used to investigate the mechanical properties of interface between AZ63 and Q235. It is shown that the hot-dip galvanization of the Q235 surface and T6 treatment were beneficial to improve the metallurgical bonding shear strength and microhardness of the interface. After T6 heat treatment, the highest shear strength at the interface between AZ63 and galvanized Q235 was up to 31.9 ± 1.9 MPa.

Objective: To investigate the safety and efficacy of low-profile visualized intraluminal support (LVIS) stent-assisted coiling of intracranial tiny aneurysms using a “compressed” stent technique.Methods: We retrospectively analyzed patients with tiny aneurysms treated in our hospital with LVIS devices using a compressed stent technique. We analyzed patients' imaging outcomes, clinical outcomes, and complications.Results: Forty-two tiny aneurysms in 42 patients were included in this study cohort; 8 patients presented with subarachnoid hemorrhage at admission. The immediate postoperative complete embolization rate was 76.2% (32/42). After an average of 8.5 months of imaging follow-up, the complete embolization rate was 90.5% (38/42), and no aneurysm recanalization occurred. After an average of 24.4 months of clinical follow-up, 95.2% (40/42) of the patients achieved favorable clinical outcomes (modified Rankin scale = 0/1). Operation-related complications occurred in two patients (4.8%); one intraoperative acute thrombosis, and one significant unilateral decreased vision during the postoperative follow-up.Conclusion: LVIS stent-assisted coiling of intracranial tiny aneurysms using a compressed stent technique is safe and effective. Combined stent compression technology is beneficial to maximize the complete embolization of aneurysms and reduce aneurysm recanalization. This study expands the clinical applicability of LVIS stents.

The Total Coloring Conjecture (TCC) states that every simple graph G is totally (Δ+2)-colorable, where Δ denotes the maximum degree of G. In this paper, we prove that TCC holds for dumbbell maximal planar graphs. Especially, we divide the dumbbell maximal planar graphs into three categories according to the maximum degree: J9, I-dumbbell maximal planar graphs and II-dumbbell maximal planar graphs. We give the necessary and sufficient condition for I-dumbbell maximal planar graphs, and prove that any I-dumbbell maximal planar graph is totally 8-colorable. Moreover, a linear time algorithm is proposed to compute a total (Δ+2)-coloring for any I-dumbbell maximal planar graph.

A domination coloring of a graph G is a proper vertex coloring of G, such that each vertex of G dominates at least one color class (possibly its own class), and each color class is dominated by at least one vertex. The minimum number of colors among all domination colorings is called the domination chromatic number, denoted by χdd(G). In this paper, we study the complexity of the k-domination coloring problem by proving its NP-completeness for arbitrary graphs. We give basic results and properties of χdd(G), including the bounds and characterization results, and further research χdd(G) of some special classes of graphs, such as the split graphs, the generalized Petersen graphs, corona products, and edge corona products. Several results on graphs with χdd(G)=χ(G) are presented. Moreover, an application of domination colorings in social networks is proposed.

Objective: To evaluate effectiveness and safety of Pipeline embolization device (PED) for large or giant verterbrobasilar aneurysms (LGVBAs), and to compare the therapeutic effects of PED with and without adjunctive coils.Methods: We retrospectively analyzed 21 cases of unruptured LGVBAs who were treated in our hospital with PED. These cases were divided into “PED group” and “PED with adjunctive coils group.” We compared the aneurysm characteristics and treatment outcomes between the two groups.Results: The overall neurological complication rate was 28.6% (6/21) and the mortality rate was 4.8% (1/21). There were 12 patients in the PED group and nine in the PED with adjunctive coils group. There were no significant differences in age, smoking, hypertension, aneurysm size, aneurysm location, or operation time between the two groups. The complete aneurysm embolization rate and favorable outcome rate (modified Rankin Scale = 0,1) of the PED with adjunctive coils group was 78% (7/9) and 100% (9/9), respectively, which were both better compared with the PED group with 63.6% (7/11) and 83% (10/12), respectively. However, these differences were not statistically significant.Conclusion: The effectiveness and safety of PED for LGVBAs is acceptable. Treatment results did not differ between the PED and PED with adjunctive coils groups; therefore, whether coils should be used may depend the operator. Our results suggest that correct use of the coils does not increase complications. We suggest that PED with adjunctive coils should be used for some selected LGVBAs.

The limitations of the Shannon entropy and the dynamic Shannon entropy are discussed. They only measure the aleatory uncertainty of stochastic processes. In this paper, based on the practical considerations, an entropy formula for measuring the uncertainty of stochastic processes is proposed, which measures not only the aleatory uncertainty but also the epistemic uncertainty. The uncertainty of the Gaussian process in four different situations is discussed. These works fill the gap between information theory and signal processing and thus can be used as a design guideline for constructing a secure source in the security field.

Despite the design of nano-structured SnO2 anodes has attracted much attention because of its high theoretical capacity, good electron mobility, and low potential of lithium-ion intercalation, challenges remain due to their weak mechanical stability, complex processing and rapid capacity decay. The one-dimensional binder-free porous CC/SnO2 nanotube arrays are synthesized with a well-suited core etching method to meet the needs of steady operation of flexible devices under mechanical deformation. This porous, binder-free nanostructure has large contact area with the electrolyte and excellent electron transport performance. The electrochemical measurements demonstrate that these nanotube arrays have high energy density and high-rate capability. After 500 cycles at a current density of 200 mA g−1, their stable capacity remains at 595.7 mA h g−1.

The performance of anodes of lithium-ion batteries relies largely on the architecture and composition of the hybrid active materials. We present a two-step, seed-free, solution-based method for the direct growth of hierarchical charantia-like TiO2/Fe2O3 core/shell nanotube arrays on carbon cloth substrates. An ultrahigh loading of the nanomaterial on carbon fibers was achieved with this method without the use of a binder. This three-dimensional porous hollow architecture and its direct contact with the CC current collector ensure an efficient electronic pathway. The hollow TiO2 framework effectively protects the hierarchical charantia-like TiO2/Fe2O3 hollow core/shell arrays from collapsing because of its negligible volume change during cycling. Meanwhile, the self-assembled α-Fe2O3 hollow nanospheres guarantee a large capacity and contact area with the electrolyte. This flexible anode with a 3D porous charantia-like hollow architecture exhibits high cycle performance, reversible capacity, and rate capability. These nanotube arrays maintain a high reversible capacity of 875 mAh g−1 after 200 cycles at a current density of 200 mA g−1. This simple, cost-effective, and scalable electrode fabrication strategy can be implemented in the fabrication of high-performance wearable energy storage devices.

Graphene-based MoS2 nanocomposites are expected to be promising anode materials for lithium ion batteries because of their large specific capacity and high conductivity. However, the aggregation of graphene and the weak interaction between the two components hinder their practical application. Inspired by the sandwich structure, novel three-dimensional flower-like MoS2-PrGO sandwich composites were proposed as an advanced anode material for lithium-ion batteries. The separated 2D ultrathin rGO nano-sheets were connected by PEO chains and assembled into a well-organized 3D layered spatial structure, which not only avoids the aggregation of graphene but also accommodates a high mass loading of the micro-scale MoS2 nano-flowers. MoS2 nano-flowers with open architecture deliver large specific area. The rGO interlayers act as a conductive framework, making all flower-like MoS2 nano-stuffing electrochemically active. The ultra-thin 2D nano-sheets provide excellent cycle stability due to their neglectable volume changes during cycling. The 3D flower-like MoS2-PrGO sandwich composites deliver high energy density, excellent conductivity and stable cyclic performance during charge-discharge process. With a nearly 100% coulombic efficiency, their reversible capacity is retained at 1,036 mA h g−1 even after 500 cycles at current densities of 100 mA g−1. This novel design strategy provides a broad prospect for the development of advanced anode materials for superior lithium storage.

The dialogue system has always been one of the important topics in the domain of artificial intelligence. So far, most of the mature dialogue systems are task-oriented based, while non-task-oriented dialogue systems still have a lot of room for improvement. We propose a data-driven non-task-oriented dialogue generator “CERG” based on neural networks. This model has the emotion recognition capability and can generate corresponding responses. The data set we adopt comes from the NTCIR-14 STC-3 CECG subtask, which contains more than 1.7 million Chinese Weibo post-response pairs and 6 emotion categories. We try to concatenate the post and the response with the emotion, then mask the response part of the input text character by character to emulate the encoder-decoder framework. We use the improved transformer blocks as the core to build the model and add regularization methods to alleviate the problems of overcorrection and exposure bias. We introduce the retrieval method to the inference process to improve the semantic relevance of generated responses. The results of the manual evaluation show that our proposed model can make different responses to different emotions to improve the human-computer interaction experience. This model can be applied to lots of domains, such as automatic reply robots of social application.

Within the context of large-scale symmetry, a study on deep vision servo multi-vision tracking coordination planning for sorting robots was conducted according to the problems of low recognition sorting accuracy and efficiency in existing sorting robots. In this paper, a kinematic model of a mobile picking manipulator was built. Then, the kinematics design of the orwX, Y, Z three-dimensional space manipulator was carried out, and a method of deriving and calculating the base position coordinates through the target point coordinates, the current moving chassis center coordinates and the determined manipulator grasping attitude conditions was proposed, which realizes the adjustment of the position and attitude of the moving chassis as small as possible. The multi-vision tracking coordinated sorting accounts 79.8% of the whole cycle. The design of a picking robot proposed in this paper can greatly improve the coordination symmetry of logistic package target recognition, detection and picking.

Abstract Propose We aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC). Methods Microarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets. Results A total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC. Conclusions ULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.

Pesticide operators are often exposed to high levels of contaminants, leading to potential adverse health impacts on these agricultural workers. In tropical regions, pesticide applicators are more vulnerable to dermal exposure than their counterparts in temperate regions. Thus, it is highly desirable to develop new spraying methods to minimize the pesticide exposure level without sacrificing the pest control efficiency. Due to their flexibility, high efficiency, and lower labor intensity, unmanned aerial vehicles (UAVs) have attracted considerable attention in precision pest management. However, the pesticide operator exposure assessment during the spraying application with UAVs, especially the comparison with conventional ground sprayers, has not been well investigated. In this work, the control effect against thrips on cowpea and operator exposure determination by aerial and ground spraying in Hainan Province were carried out and compared. When biopesticide spinetoram with the same dosage was applied, the field control efficacy against cowpea thrips sprayed by UAVs was higher than that of knapsack electric sprayers. Moreover, UAV spraying could greatly reduce water consumption and working time. For UAV spraying, when the amounts of water applied per hectare were 22.5, 30, and 37.5 L, the control effects on thrips on the first day were about 69.79%, 80.15%, and 80.58%, respectively. When Allura Red as a pesticide surrogate was applied under similar spraying scenarios with the field control against thrips on cowpea, the average total unit exposure of the knapsack operator (1952.02 mg/kg) was greatly higher than that of the UAV operator (134.51 mg/kg). The present research indicates that plant protection UAV is the direction of development of modern intensive sustainable agriculture.

Abstract The present study provides an integrated view of algal removal of the antibiotic ceftazidime and its basic parent structure 7-aminocephalosporanic acid (7-ACA), including contribution analysis, bacteriostatic and aquatic toxic assessment and metabolite verification. 92.70% and 96.07% of the two target compounds was removed after the algal treatment, respectively. The algal removal can be separated into three steps: a rapid adsorption, a slow cell wall-transmission and the final biodegradation. Additionally, while ceftazidime demonstrated an excellent inhibitory effect on Escherichia coli, there was no bacteriostasis introduced after the algal treatment, which could avoid favoring the harmful selective pressure. On the other hand, no significant aquatic impact of the two target compounds on rotifers was observed and it was not enhanced after the algal treatment. To better reveal the mechanism involved, metabolite analyses were performed. Δ-3 ceftazidime and trans-ceftazidime were regarded as the metabolites of ceftazidime and the metabolite of 7-ACA was regarded as a compound which shared the similar structure with 4-chlorocinnamic acid. Our study indicated that the green algae performed a satisfactory growth capacity and played a dominant role for the biodegradation of the target antibiotics, which achieved high removal efficiency and low environmental impact.

Neuropeptide FF (NPFF) is a family member of RF-amide peptides, which are suggested to be involved in the control of vertebrate feeding behavior. However, little is known about the effect of the NPFF peptide on feeding-related processes in basal vertebrates. In this study, four full-length cDNAs, npff, npffr1, npffr2-1, and npffr2-2, were cloned from spotted sea bass and characterized. The conserved NPFF peptide is biologically active because it functionally interacts with different receptors expressed in cultured eukaryotic cells to enhance CRE promoter activity. Tissue distribution analysis showed that the highest npff mRNA expression occurred in the telencephalon, hypothalamus, medulla, gonad and muscle, but the npffrs mRNAs were mainly distributed within the central nervous system (CNS). In situ hybridization (ISH) detected npff-expressing cells in several specific regions ranging across the telencephalon and midbrain to the hypothalamus. Incubation of the spotted sea bass conserved NPFF peptide significantly increased the expression of orexin (orx) and neuropeptide Y (npy) mRNA and decreased the expression of leptin (lep), somatostatin (ss), and cholecystokinin (cck) mRNA in brain cells. Similarly, the conserved NPFF peptide also heightened the expression of gastrin (gas), ghrelin (ghrl), and motilin (mtl) mRNA and significantly reduced the expression of cck mRNA in the intestine and stomach. Taken together, these data suggest that the NPFF peptide may play a stimulating role in regulating feeding-related processes in spotted sea bass.

Neurokinin B (NKB) is a member of the tachykinin (tac) family that plays important roles in mammalian growth by modulating prolactin (PRL) synthesis and secretion and causing contraction of the stomach and intestine. However, its potential role in regulating growth of teleosts is less clear. We aimed to explore the role that NKB plays in regulating fish growth using the spotted sea bass (Lateolabrax maculatus) as a model. In the present study, two tac3 and two tacr3 genes were identified in the spotted sea bass. Sequence analysis showed that two tac3 transcripts, tac3a and tac3b, encode four NKBs: NKBa-13, NKBa-10, NKBb-13, and NKBb-10. Expression analysis in different tissues showed that both genes are highly expressed in the brain, stomach and intestine of the spotted sea bass. In situ hybridization indicated that the tac3a and tac3b mRNAs are both localized in several brain regions, such as the telencephalon and hypothalamus, and that tacr3a and tacr3b are localized in the intestinal villus and gastric gland. To investigate the potential role of NKBs in regulating growth, in vitro experiments were performed to detect the effect of NKBs on growth-related gene expression in the brain and brain-gut peptide (BGP)-related genes in the stomach and intestine. NKBb-13 was the most critical ligand in regulating the expression of growth-related genes in the brain and brain-gut peptide (BGP)-related genes in the stomach. The expression of cholecystokinin (cck) was enhanced by NKBa-13, NKBa-10, and NKBb-10 but not NKBb-13 in the intestine. In general, our results showed that NKBs participate in regulating the growth of spotted sea bass.