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Dietary alkaloid nuciferine isolated from the leaves of Nelumbo nucifera can ameliorate dyslipidemia and liver lipid accumulation, but the underlying mechanism remains unclear.

Early detection of cancer can effectively improve the survival rate of cancer patients. Fluorescence imaging has the advantages of high sensitivity and rapid imaging, and is widely used in the precise imaging detection of tumors. In this study, five kinds of Au-rare earth bimetallic nanoclusters (Au/Ln NCs) were prepared by template method using five representative rare earth elements doped with gold. The morphologies, surface charges, sizes, fluorescence quantum yields and maximum fluorescence emission wavelengths of these five kinds of Au/Ln NCs were characterized and contrasted. The findings indicated that the Au/Ce nanoclusters (Au/Ce NCs) prepared by Ce doping have the longest fluorescence emission wavelength (695 nm) and higher quantum yield, which could effectively avoid the interference of autofluorescence, and was suitable for fluorescence imaging of tumor cells. In order to improve the specific accumulation of nanoclusters in tumor cells, Au/Ce NCs were coated with folic acid modified liposomes (lip-FA) to constructed a targeted fluorescent imaging probe with near-infrared response (Au/Ce@lip-FA), which was successfully used for fluorescence imaging of tumor cells. The probe has the characteristics of stable fluorescence signal, good targeting, easy internalization, and safe metabolism, and can provide high-resolution and high-brightness imaging information, which is expected to play an important role in the clinical diagnosis and surgical treatment of tumors.

Montmorillonite (MMT) coated with roughened noble metal nanoparticles are novel hybrid nanocomposite with a wide range of applications including agriculture, materials science and biomedical engineering. Herein, we developed a hybrid nanocomposite (MMT/AgNPs) based on MMT coated with silver nanoparticles (AgNPs), which can be used as a cost-effective and efficient surface-enhanced Raman spectroscopy (SERS) substrate for the detection of pesticides in fruits and vegetables. MMT itself is negatively charged and can be assembled with positively charged AgNPs through electrostatic interactions. Moreover, MMT has a layered 2D structure that possesses a large surface area, which can load a large number of AgNPs to form more SERS hotspots for the ultrasensitive measurement. SERS performance of the MMT/AgNPs nanocomposite was tested by 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and the substrate can obtain the strongest SERS enhancement effect with the volume ratio of MMT/AgNPs of 1 : 10. These substrates were applied in the measurement of thiram in apples and spinach samples by SERS. Detection limits of pesticide molecules of 5.0 × 10

BACKGROUND: Vascular invasion is an important risk factor of poor prognosis in hepatocellular carcinoma (HCC) patients. The detection of circulating tumor cells (CTCs) in the blood is direct evidence of tumor presence. There are few reports on CTCs and metastasis and vascular invasion of HCC. The purpose of this study was to analyze the significance of CTCs in the portal vein regarding metastases and vascular invasion in HCC patients. METHODS: A total of 104 HCC patients diagnosed and treated in Zhengzhou University People’s Hospital were enrolled. Surgery was performed in 60 individuals. Portal vein blood samples were collected before treatment for CTCs detection. We used the isolation by size of epithelial tumor cells (ISET) and fluorescence in situ hybridization (FISH) to enrich and classify CTCs from blood samples. The patients were divided into metastasis and nonmetastasis groups according to the metastasis status before treatment. Differences in clinical indicators such as alpha-fetoprotein (AFP) levels, tumor size, CTCs count, and macrovascular tumor thrombus between the two groups were analyzed as well as the associations of CTCs count with the above indicators. For individuals with postoperative pathology, the relationship between CTCs counts and microvascular invasion (MVI) was analyzed. RESULTS: The amounts of portal vein CTCs were higher in patients with metastases compared with the nonmetastases group (20 vs. 7; z=3.795; P

Platelets, small hemostatic blood cells, are derived from megakaryocytes (MKs). It is accepted that both bone marrow (BM) and lung are principal sites of thrombogenesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate platelets, and retain their functionality, is poor at present. Here we show that perfusion of MKs ex vivo through the mouse lung vasculature generates substantial platelet numbers, up to 3,000 per MK. Despite their large size, MKs were able repeatedly to passage through the lung vasculature, leading to enucleation and subsequent platelet generation intravascularly. Using the ex vivo lung and a novel in vitro microfluidic chamber we determined how oxygenation, ventilation and endothelial cell health support platelet generation. Our data also show a critical role for the actin regulator TPM4 in the final steps of platelet formation in lung vasculature. The findings could inform new approaches to large scale generation of platelets.

In knowledge graph reasoning, the existing graph attention mechanisms tend to distribute attention to certain high-frequency relations. In this work, we design a target relational attention-oriented reasoning model, which focuses more on the relations that match the target relation. We propose a hierarchical (node-level and relational subgraph-level) attention mechanism to aggregate the information of multi-hop neighbors, and to thereby obtain a better node-embedding representation, (with high-order propagation characteristics). The mechanism also relieves over-smoothing to a certain extent. Node-level information aggregation uses the classical graph-attention mechanism, and the distribution of attention in the subgraph-level information aggregation is determined according to the relation in the reasoning task. In other words, we must give these relations different attentions according to the reasoning relation in the task. Experiments show that our model significantly outperforms current state-of-the-art methods. We further study the influence of encoder parameters on the model performance; increasing the number of attention-heads, layers, or hidden out-dimensions can effectively improve the performance.

A cascade-arch-firing low-NOx and high-burnout configuration (CLHC) is developed to strengthen low-NOx combustion and maintain high burnout in down-fired furnaces. Numerical simulations of the in-furnace flow field, coal combustion, and NOx formation are performed in a 600 MWe down-fired furnace to evaluate the staged-air location's effect on the low-NOx and high-burnout performance. The furnace, which is in service with a deep-air-staging multi-injection and multi-stage combustion technology (MIMSCT), was modified with the CLHC combustion system for the present simulations. Various staged-air location coefficients of CH = 0.65, 0.70, 0.75 and 0.80 were analysed. Moving downward staged-air to enlarge CH initially improves but then deteriorates the in-furnace flow-field symmetry. Similar changes in the gas temperature and species distribution patterns in the furnace are evident. As CH increases from 0.65 to 0.75, levels of the residual O2 concentration, carbon content in fly ash, and NOx emissions at the furnace outlet decline continuously. The highest setting CH = 0.80 generates severely asymmetric combustion accompanied by poor performance indexes, raising the unburnt rate and NOx emissions by 20–30%. The staged-air location of CH = 0.75 achieves a symmetric flow-field pattern, satisfactory low NOx emissions of ~670 mg/m3 at 6% O2 and high-burnout performance with carbon in fly ash of 5%. NOx emissions are reduced by 26% without affecting burnout in comparison to the currently advanced deep-air-staging MIMSCT.

Dysplasia and intramucosal esophageal squamous cell carcinoma (ESCC) frequently go unnoticed with white-light endoscopy and, therefore, progress to invasive tumors. If suitable targets are available, fluorescence molecular endoscopy might be promising to improve early detection. Microarray expression data of patient-derived normal esophagus (n = 120) and ESCC samples (n = 118) were analyzed by functional genomic mRNA (FGmRNA) profiling to predict target upregulation on protein levels. The predicted top 60 upregulated genes were prioritized based on literature and immunohistochemistry (IHC) validation to select the most promising targets for fluorescent imaging. By IHC, GLUT1 showed significantly higher expression in ESCC tissue (30 patients) compared to the normal esophagus adjacent to the tumor (27 patients) (p &lt, 0.001). Ex vivo imaging of GLUT1 with the 2-DG 800CW tracer showed that the mean fluorescence intensity in ESCC (n = 17) and high-grade dysplasia (HGD, n = 13) is higher (p &lt, 0.05) compared to that in low-grade dysplasia (LGD) (n = 7) and to the normal esophagus adjacent to the tumor (n = 5). The sensitivity and specificity of 2-DG 800CW to detect HGD and ESCC is 80% and 83%, respectively (ROC = 0.85). We identified and validated GLUT1 as a promising molecular imaging target and demonstrated that fluorescent imaging after topical application of 2-DG 800CW can differentiate HGD and ESCC from LGD and normal esophagus.

Fluoride pollution is widely present in the living environment. As a critical period of brain development, the perinatal period is extremely vulnerable to fluoride. Studies have found that choline can protect the brain's memory and enhance the ability to focus. However, the effect of choline on perinatal fluoride-induced nerve damage remains unclear. Therefore, 32 Kunming newly conceived female mice and their offspring mice were randomly divided into control, NaF, LC + NaF, and HC + NaF groups, and the HE staining, Y-maze test, RT-PCR, western blotting, immunohistochemistry, etc. were used in this study. The results showed that fluoride decreased the brain organ coefficients and brain protein content (p 0.05, p 0.01), and caused histomorphological damage in the hippocampus and cortex, which suggested that fluoride affected the development of the brain and damaged the brain. Moreover, the results of the Y-maze test showed that fluoride increased the number of learning days, error reaction time, and total reaction time, and decreased the AchE activity in the brain (p 0.05, p 0.01), which indicated that fluoride reduced the learning and memory ability of the mice. Besides, the results showed that fluoride decreased the mRNA and protein expression levels of α4β2 nAChRs and α7 nAChRs in the hippocampus and cortex (p 0.05, p 0.01). However, perinatal choline supplementation reversed the aforementioned fluoride-induced changes. In short, these results demonstrated that choline alleviated perinatal fluoride-induced learning and memory impairment, which will provide a rationale for the mitigation and prevention of fluoride-induced brain damage.

Ovarian cancer is one of the most lethal gynecologic malignancies for women. Due to the lack of efficient target therapy, the overall survival rate for patients with advanced ovarian cancer is still low. Illustrating the molecular mechanisms dictating ovarian cancer progression is critically important to develop novel therapeutic agents. Here, we found that RNA-binding motif protein 11 (RBM11) was highly elevated in ovarian cancer tissues compared with normal ovary, while RBM11 depletion in ovarian cancer cells resulted in impaired cell growth and invasion. Moreover, knockdown of RBM11 also retarded tumor growth in the A2780 ovarian cancer xenograft model. Mechanically, we found that RBM11 positively regulated Akt/mTOR signaling pathway activation in ovarian cancer cells. Thus, these results identify RBM11 is a novel oncogenic protein and prognostic biomarker for ovarian cancers.

To solve the problem of the serious mileage reduction of electric vehicles in winter, this paper introduces a new type of motor with eddy current braking and heating system (EBHS). EBHS can convert the vehicle’s kinetic energy into the thermal energy which can be used for heating the cabin and the battery at the right temperature. This paper proposes the structural layout and operating modes with the novel motor. The air gap magnetic density of the ECR is calculated by the magnetic circuit method. The braking torque is solved by the transient electromagnetic finite element method. The eddy current loss power at different speeds is used for analyzing heat performance. Based on MATLAB/Simulink environment, the fuzzy control method is used to simulate the EBHS’s braking energy efficiency. Compared with PTC heating, the power consumption of the new motor is reduced by 25 % and the cabin can reach 20 °C in 160 seconds. Finally, it is verified by bench test that the retarder stator stayed within 110 °C when it is continuously operated for 12 minutes. The braking torque of the finite element analysis result meet the test value, and the error rate is not higher than 11.7 %.

Hydrogels have excellent biocompatibility, transparency, stretchability, and ionic conductivity, but their fabrication through photopolymerization-based 3D printing is limited due to the low solubility of hydrophobic photoinitiators and lack of efficient hydrophilic photoinitiators. Herein, a type of microemulsion is synthesized and the common hydrophobic photoinitiator can be adopted and finally, a series of transparent hydrogels with high strength (up to 22.9 MPa), elasticity (up to 583%), and ionic conductivity (up to 9.64 S m-1) are fabricated through digital light processing 3D printing technology. Objects with complex structures and a high printing resolution are printed. Hydrogels with both high strength and high ionic conductivity are obtained through chemical crosslinking and ion coordination effect. Dual-material 3D printing is applied to package the hydrogel with elastomers. Due to the high sensitivity and reliability under both stretching and compressive deformation, the hydrogel sensors are applied to monitor various human motions. In addition, the hydrogel exhibits solvent-induced dehydration and excellent water-activated shape memory properties, which are greatly beneficial for its storage and applications in the biomedical field.

The purpose of the paper is to investigate the impact of university-industry collaborative research with different dimensions on university patent commercialisation and offer suggestions to promote...

Introduction In the present study, ternary deep eutectic solvent-based ultrasound-assisted extraction was developed for the efficient extraction of plantamajoside, acteoside, quercetin and kaempferol from Plantago asiatica L. Methodology Six kinds of choline chloride-based ternary deep eutectic solvents (TDESs) were prepared as potential extraction solutions. In order to obtain optimal extraction efficiency, a series of extraction conditions were investigated by single-factor test and orthogonal test. Results The extraction efficiency of choline chloride/lactic acid/ethylene glycol (ChCl-LA-EG) was much higher than that of other TDESs. ChCl-LA-EG-11 synthesised with choline chloride, lactic acid and ethylene glycol (1:4:2) was considered to have a higher extraction efficiency. The optimal ultrasound-assisted extraction conditions were as follows: water content in ChCl-LA-EG-11, 50%; extraction temperature, 70°C; ratio of solid/liquid, 20 mg/mL; ultrasonic power, 60 W; extraction time, 35 min; pH of the solution, 8. Under the optimal extraction conditions, the extraction efficiencies of plantamajoside, acteoside, quercetin and kaempferol were 3.83 ± 0.41, 4.23 ± 0.45, 0.56 ± 0.15 and 0.19 ± 0.08 mg/g, respectively. The extraction efficiency of the total target components was 9.21 ± 0.63 mg/g, which was much higher than that of conventional solvents (water, methanol, ethanol, 50% methanol, 50% ethanol). The target components were isolated efficiently from the TDES solution by an AB-8 macroporous resin column with a recovery rate of 95.6%. Conclusion This study demonstrated that TDESs possessed excellent physical and chemical properties and had enormous potential for active component extraction of traditional Chinese medicinal materials.

A simple high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed for the determination of 3-bromopyruvate (3-BrPA) in rat plasma for the first time. The analytes were separated on a C

A type of polyurethane elastomer with excellent self-healing ability has been fabricated through digital light processing 3D printing. First, a type of polyurethane acrylate containing disulfide bonds is synthesized and then compounded with reactive diluent and photoinitiators to get a photopolymer resin. Due to the good fluidity and high curing rate, the photopolymer resin can be applied in DLP 3D printing, and various 3D objects with complicated structures, high printing accuracy, and remarkable self-healing ability have been printed. The tensile strength and elongation at break of the polyurethane elastomer are 3.39 ± 0.09 MPa and 400.38 ± 14.26%, respectively, and the healing efficiency can get to 95% after healing at 80 °C for 12 h and can be healed for multiple times. With the ease of fabrication and excellent performance, the polyurethane elastomers from DLP 3D printing have great potential applications in flexible electronics, soft robotics, and sensors.

Knowledge graphs’ reasoning is of great significance for the further development of artificial intelligence and information retrieval, especially for reasoning over temporal knowledge graphs. The rotation-based method has been shown to be effective at modeling entities and relations on a knowledge graph. However, due to the lack of temporal information representation capability, existing approaches can only model partial relational patterns and they cannot handle temporal combination reasoning. In this regard, we propose HTTR: Householder Transformation-based Temporal knowledge graph Reasoning, which focuses on the characteristics of relations that evolve over time. HTTR first fuses the relation and temporal information in the knowledge graph, then uses the Householder transformation to obtain an orthogonal matrix about the fused information, and finally defines the orthogonal matrix as the rotation of the head-entity to the tail-entity and calculates the similarity between the rotated vector and the vector representation of the tail entity. In addition, we compare three methods for fusing relational and temporal information. We allow other fusion methods to replace the current one as long as the dimensionality satisfies the requirements. We show that HTTR is able to outperform state-of-the-art methods in temporal knowledge graph reasoning tasks and has the ability to learn and infer all of the four relational patterns over time: symmetric reasoning, antisymmetric reasoning, inversion reasoning, and temporal combination reasoning.

Short-range semiochemicals convey individual-specific information, which is important for final successful courtship and copulation. In this study, an electroantennography (EAG) instrument was used to determine the legs of male Bactrocera dorsalis that might participate in the perception of 4-allyl-2,6-dimethoxyphenol (4-DMP), a female-biased cuticular hydrocarbon (CHC) component. By performing comparative RNA-seq analysis, nine differentially expressed OBPs between 4-DMP-stimulated (M4-DMP) and unstimulated (M) male flies were screened out. Among the four downregulated OBPs, BdorOBP2 exhibited the strongest binding to 4-DMP than BdorOBP4, BdorOBP19a, and BdorOBP56h. Functional analyses confirmed that the reduction in transcript abundance of BdorOBP2 led to a significant decrease in behavioral responses of male flies to 4-DMP. In silico simulation revealed dramatic changes in the key residues and conformation between the two complexes, implying that BdorOBP2 might activate different receptors after binding to 4-DMP or methyl eugenol (ME). The results of this study suggest that BdorOBP2 mediates behavioral responses to 4-DMP and could be a promising molecular target for strategies of pest control.

Farfarae Flos is a traditional Chinese medicine that has long been used to treat allergies. In this study, we aimed to investigate the effect of a petroleum extract of Farfarae Flos (PEFF) in a mouse model of allergic rhinitis (AR) and to explore the underlying molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with ovalbumin (OVA). PEFF was administered intranasally and AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The mechanism of action of PEFF was evaluated by histological analysis of nasal mucosa architecture and inflammatory status; ELISA-based quantification of serum OVA-specific IgE, interferon-γ (IFN-γ), and interleukin-4 (IL-4) concentrations; and immunohistochemical and western blot analysis of T-bet and GATA3 protein expression in nasal mucosa and spleen tissues. The results showed intranasal administration of PEFF alleviated AR symptom scores and reduced both the infiltration of inflammatory cells and tissue damage in the nasal mucosa. PEFF significantly decreased serum concentrations of OVA-specific IgE (P

High-rate battery-type cathode materials have attracted wide attention for advanced battery-supercapacitor hybrid (BSH) devices. Herein, a core-shell structure of the hollow mesoporous carbon spheres (HMCS) supported NiSe2 nanosheets (HMCS/NiSe2) is constructed through two-step reactions. The HMCS/NiSe2 shows a max specific capacity of 1,153.5 C·g−1 at the current density of 1 A·g−1, and can remain at 774.5 C·g−1 even at 40 A·g−1 (the retention rate as high as 67.1%) and then the HMCS/NiSe2 electrode can keep 80.5% specific capacity after 5,000 cycles at a current density of 10 A·g−1. Moreover, the density functional theory (DFT) calculation confirmed that the introduction HMCS into NiSe2 made adsorption/desorption of OH− easier, which can achieve higher rate capability. The HMCS/NiSe2//6 M KOH//HMCS hybrid device has energy density of 47.15 Wh·kg−1 and power density of 801.8 W·kg−1. This work provides a feasible electrode material with a high rate and its preparation method for high energy density and power density energy storage devices.

Simple Summary: Barrett's esophagus (BE) is the precursor of esophageal adenocarcinoma (EAC). Dysplastic BE (DBE), including low-grade dysplasia (LGD) and high-grade dysplasia (HGD), shows a higher progression risk to EAC compared to non-dysplastic BE (NDBE). If LGD or HGD is detected, more intensive endoscopic surveillance or endoscopic treatment is recommended. This results in a significantly improved prognosis compared to EACs treated by surgery and/or chemoradiotherapy. However, the miss rates for detecting DBE by endoscopy remain high. Fluorescence molecular endoscopy (FME) can fill this gap by targeting the tumor-specific expression of proteins. This study aimed to identify target proteins suitable for FME. We identified SPARC, SULF1, PKC iota, and DDR1 as promising imaging targets for FME to differentiate DBE from NDBE tissue. We are also the first to develop near-infrared fluorescent tracers, SULF1-800CW and SPARC-800CW, for the endoscopic imaging of DBE tissue.Abstract: Barrett's esophagus (BE) is the precursor of esophageal adenocarcinoma (EAC). Dysplastic BE (DBE) has a higher progression risk to EAC compared to non-dysplastic BE (NDBE). However, the miss rates for the endoscopic detection of DBE remain high. Fluorescence molecular endoscopy (FME) can detect DBE and mucosal EAC by highlighting the tumor-specific expression of proteins. This study aimed to identify target proteins suitable for FME. Publicly available RNA expression profiles of EAC and NDBE were corrected by functional genomic mRNA (FGmRNA) profiling. Following a class comparison between FGmRNA profiles of EAC and NDBE, predicted, significantly upregulated genes in EAC were prioritized by a literature search. Protein expression of prioritized genes was validated by immunohistochemistry (IHC) on DBE and NDBE tissues. Near-infrared fluorescent tracers targeting the proteins were developed and evaluated ex vivo on fresh human specimens. In total, 1976 overexpressed genes were identified in EAC (n = 64) compared to NDBE (n = 66) at RNA level. Prioritization and IHC validation revealed SPARC, SULF1, PKC iota, and DDR1 (all p < 0.0001) as the most attractive imaging protein targets for DBE detection. Newly developed tracers SULF1-800CW and SPARC-800CW both showed higher fluorescence intensity in DBE tissue compared to paired non-dysplastic tissue. This study identified SPARC, SULF1, PKC iota, and DDR1 as promising targets for FME to differentiate DBE from NDBE tissue, for which SULF1-800CW and SPARC-800CW were successfully ex vivo evaluated. Clinical studies should further validate these findings.

Colorectal cancer (CRC) is a major leading cause of cancer mortality worldwide in which dysregulated protein synthesis plays an etiologic role. The eukaryotic elongation factor 1 A1 (eEF1A1) exerts significant effects on protein synthesis by contributing to peptide chain extension. Whereas its role in CRC remains to be investigated. In this study, we found that the mRNA and protein levels of eEF1A1 were significantly upregulated in CRC cell lines and tissues. Elevated expression of eEF1A1 was correlated with shorter overall survival in 94 CRC patients. The inhibition of proliferation and cell cycle block were observed in CRC cells after eEF1A1 downregulation. Mechanistically, weighted gene correlation network analysis and further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that mitogen-activated protein kinases (MAPKs) signaling pathways were significantly enriched in high-eEF1A1 expression group, and the levels of phosphorylated p38/JNK/ERK MAPK were dramatically decreased after eEF1A1 downregulation. Overexpression of eEF1A1 in CRC correlated with a poor prognosis. Collectively, this study determined the oncogenic role of eEF1A1 in CRC proliferation and tumorigenesis. eEF1A1 might be a promising therapeutic target and prognostic biomarker in CRC.

Background: Esophageal adenocarcinoma (EAC) is one of the main causes of cancer-related deaths worldwide and its incidence is rising. Barrett’s esophagus (BE) can develop low- and high-grade dysplasia which can progress to EAC overtime. The golden standard to detect dysplastic BE (DBE) or EAC is surveillance with high-definition white-light endoscopy (HD-WLE) and random biopsies according to the Seattle protocol. However, this method is time-consuming and associated with a remarkable miss rate. Therefore, there is great need for the development of novel reliable techniques to optimize surveillance strategies and improve detection rates. Summary: Optical chromoendoscopy (OC) techniques like narrow-band imaging have shown improved detection of DBE and EAC compared to HD-WLE and random biopsies. Most recent OC techniques, including the iSCAN optical enhancement system and linked color imaging, showed improved characterization of DBE and EAC retrospectively. Fluorescence molecular endoscopy (FME) presented promising results to highlight DBE and EAC. Moreover, with the establishment of well-performing delineation computer-aided detection (CAD) algorithms and the first real-time CAD system for EAC, we expect clinical application of CAD in the near future. Key Messages: Despite impressive progress made in the development of advanced endoscopic techniques, combined HD-WLE/OC followed by random biopsies remains the golden standard for BE surveillance. Surveillance depends on appropriate mucosal cleansing, sufficient inspection time, and competence of the performing gastroenterologist to improve detection of EAC. In addition, to facilitate the clinical implementation of advanced endoscopic techniques, multicenter prospective clinical studies are demanded for OC and FME. Meanwhile, further optimization of CAD algorithms, the education of gastroenterologists, and analysis of the interaction between the clinician and the computer should be performed.

To conduct network meta-analysis (NMA) of clinical efficacy and safety of single-dose antiviral drugs, grouped by dosage, in treatment of influenza. Systematic retrievals were conducted in databases, including Pubmed, Embase, Web of Science, the Cochrane Register of Clinical Trials and from the website ClinicalTrials.gov, for clinical trials recorded between the interception of the databases and March 31, 2021. Randomized controlled trials (RCTs) of influenza treatment in which single-dose antiviral drugs were administered were selected according to preset inclusion and exclusion criteria by two researchers who screened the literature independently from each other. The quality of the included studies was assessed using the Cochrane bias risk assessment tool. Software such as Stata 16.0 and Review Manager 5.3 was adopted for statistical analysis. Pairwise meta-analysis and NMA were carried out under the random-effects model. For both binary and continuous variables, odds ratio (OR), mean difference (MD) and their 95% confidence intervals (CI) were used to rank treatment efficiencies and analyze the differences. A total of 12 RCTs involving 7296 participants were included in the analysis. According to the NMA results, peramivir 300 mg (MD = -17.68, 95% CI: [-34.05, -1.32]), peramivir 600 mg (MD = -16.15, 95% CI: [-29.35, -2.95]), baloxavir (MD = -14.67, 95% CI: [-26.75, -2.58]) and laninamivir 40 mg (MD = -12.42, 95% CI: [-22.53, -2.31]) remarkably outperformed laninamivir 20 mg in time to alleviation of symptoms (TTAS). However, no intervention statistically outperform others in antipyretic time, virus titer variations against the baseline 24 and 48 h after medication and adverse events (AEs). The efficacy rankings were: peramivir 300 mg (the surface under the cumulative ranking curve [SUCRA] = 80.3%) peramivir 600 mg (SUCRA = 76.2%) baloxavir (SUCRA = 68.4%) laninamivir 40 mg (SUCRA = 55.0%) laninamivir 20 mg (SUCRA = 16.6%) for TTAS; baloxavir (SUCRA = 76.3%) peramivir 600 mg (SUCRA = 67.8%) laninamivir 40 mg (SUCRA = 47.2%) laninamivir 20 mg (SUCRA = 40.0%) for antipyretic time; baloxavir (SUCRA = 96.7%) peramivir 300 mg (SUCRA = 64.5%) ≈ peramivir 600 mg (SUCRA = 63.2%), baloxavir (SUCRA = 93.2%) peramivir 600 mg (SUCRA = 64.0%) ≈ peramivir 300 mg (SUCRA = 55.0%), for virus titer variations against the baseline 24 and 48 h after medication, respectively; and baloxavir (SUCRA = 83.4%) peramivir 300 mg (SUCRA = 71.4%) laninamivir 20 mg (SUCRA = 62.4%) peramivir 600 mg (SUCRA = 56.2%) laninamivir 40 mg (SUCRA = 36.8%) for adverse events. Among the single-dose anti-influenza virus drugs compared, peramivir is superior to baloxavir and laninamivir in TTAS, whereas baloxavir has the best efficacy in antipyretic time, virus titer variations against the baseline 24 and 48 h after medication and AEs. This study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO), with a registration number of CRD42021238220.

Multi-source knowledge fusion is one of the important research topics in the fields of artificial intelligence, natural language processing, and so on. The research results of multi-source knowledge fusion can help computer to better understand human intelligence, human language and human thinking, effectively promote the Big Search in Cyberspace, effectively promote the construction of domain knowledge graphs (KGs), and bring enormous social and economic benefits. Due to the uncertainty of knowledge acquisition, the reliability and confidence of KG based on entity recognition and relationship extraction technology need to be evaluated. On the one hand, the process of multi-source knowledge reasoning can detect conflicts and provide help for knowledge evaluation and verification; on the other hand, the new knowledge acquired by knowledge reasoning is also uncertain and needs to be evaluated and verified. Collaborative reasoning of multi-source knowledge includes not only inferring new knowledge from multi-source knowledge, but also conflict detection, i.e. identifying erroneous knowledge or conflicts between knowledges. Starting from several related concepts of multi-source knowledge fusion, this paper comprehensively introduces the latest research progress of open-source knowledge fusion, multi-knowledge graphs fusion, information fusion within KGs, multi-modal knowledge fusion and multi-source knowledge collaborative reasoning. On this basis, the challenges and future research directions of multi-source knowledge fusion in a large-scale knowledge base environment are discussed.

Elm seed-like nickel sulfide nanosheets grown on the surface of coal-based carbon fibers are reasonably constructed and prepared by a multistep transformation approach. The silica/coal-based carbon fibers are obtained via electrospinning a water/N,N-dimethylformamide two-phase solution of oxidized coal, polyvinyl alcohol and tetraethyl orthosilicate, followed by carbonization. The elm seed-like nickel silicate nanosheets formed by many small nickel silicate nanosheets are deposited on the surface of the coal-based carbon fibers, and then transformed into nickel sulfide with a similar morphology by chemical conversion. Benefiting from the large specific surface area and unique novel structure of the obtained sample, the obtained binder-free electrode exhibits a high specific capacitance of 635.1 F g−1 at 1 A g−1 and delivers a good capacitance retention of 96.4% over 5000 cycles, which are much higher than those of the reference sample without tetraethyl orthosilicate (298.5 F g−1 and 87.7%, respectively). This design idea offers a new strategy for the synthesis of elm seed-like nickel sulfide nanosheet/coal-based carbon fiber composites as flexible electrode materials.

Carbonic anhydrase (CA) inhibitors have a long history of safe clinical use as mild diuretics, in the treatment of glaucoma and for altitude sickness prevention. In this study, we aimed to determine if CA inhibition may be an alternative approach to control thrombosis. We utilized a high-resolution dynamic imaging approach to provide mechanistic evidence that CA inhibitors may be potent anti-procoagulant agents in vitro and effective anti-thrombotics in vivo. Acetazolamide and methazolamide, while sparing platelet secretion, attenuated intracellular chloride ion entry and suppressed the procoagulant response of activated platelets in vitro and thrombosis in vivo. The chemically similar N-methyl acetazolamide, which lacks CA inhibitory activity, did not affect platelet procoagulant response in vitro. Outputs from rotational thromboelastometry did not reflect changes in procoagulant activity and reveal the need for a suitable clinical test for procoagulant activity. Drugs specifically targeting procoagulant remodeling of activated platelets, by blockade of carbonic anhydrases, may provide a new way to control platelet-driven thrombosis without blocking essential platelet secretion responses.

Molybdenum trioxide (MoO3), which possesses unique layered nanostructure and high theoretical capacity, is currently under comprehensive research as one of the most promising lithium-ion anode materials. However, MoO3 suffers from sluggish electrode reaction kinetics and huge volume expansion, causing severe capacity fading during cycling processes. Herein, ultrafine MoO3 anchored in coal-based carbon fiber to form nanocomposites (MoO3/CCNFs) was prepared by electrospinning. The unique structure of the ultrafine MoO3 nanoparticles (1–3 nm) homogeneously embedded in coal-based carbon nanofibers showed advantages of short Li+ diffusion distance, fast reaction kinetics and reduced volume expansion. The specific surface area and pore volume of MoO3/CCNFs were increased induced by small molecular gas released during carbonization of the coal, which can supply more beneficial transport routes for electrolyte ions and relieve volume stress caused by Li+ insertion. Among all samples, 0.5-MoO3/CCNFs (the addition of coal was 0.5 g) exhibited excellent conductivity. As an anode for lithium storage, the 0.5-MoO3/CCNFs showed remarkable electrochemical properties with a high specific capacity of 801.1 mA h g−1 at 0.5 A g−1 after 200 cycles, as well as excellent rate capability. This work indicates that coal-based carbon nanofibers will allow further development in high performance MoO3 electrodes.

Platelets are small anucleate blood cells1,2 with critical roles in haemostasis, thrombosis, inflammation, vascularization, innate immunity and tissue regeneration3,4. In vitro-derived platelets, as an alternative to native platelets, are attractive for fundamental research because of their rapid genetic tractability, as vectors for drug and genetic component delivery5 and in clinical platelet transfusion. At present, however, their very low production rate, and poor agonist responsiveness, are major obstacles. Platelets are formed by fragmentation from mature polyploid megakaryocytes (MKs), their precursor cells6, although the process of their generation remains incompletely understood7,8. Bone marrow is proposed to be the main site of platelet production, however indirect evidence since the 1930s9,10 and recent direct observation11 has shown that the lung can also be a primary site of platelet biogenesis. Here we established an ex vivo mouse heart-lung model (Fig. 1a) through which we were able to perfuse murine MKs. Remarkably, we could show for the first time that MKs, despite their large size, can pass multiple times through the lung vasculature, and that this leads to the generation of very large numbers of fully functional platelets (up to 3,000 per megakaryocyte7,12). Using this system and a novel in vitro microfluidic chamber we show roles for ventilation, oxygenation and healthy pulmonary endothelial cells in platelet generation. We show that MKs undergo enucleation upon repeated passage through pulmonary vasculature before fragmentation to generate platelets, with this final process dependent on the actin regulator TPM4. This advances our understanding of platelet formation in the body and establishes a novel approach to generate large numbers of them outside the body.

A total of 27 rose thaumatin-like protein (TLP) genes were identified from the rose genome through bioinformatics analyses. RcTLP6 was found to confer salinity stress tolerance in rose. Thaumatin-like proteins (TLPs) play critical roles in regulating many biological processes, including abiotic and biotic stress responses in plants. Here, we conducted a genome-wide screen of TLPs in rose (Rosa chinensis) and identified 27 RcTLPs. The identified RcTLPs, as well as other TLPs from six different plant species, were placed into nine groups based on a phylogenetic analysis. An analysis of the intron–exon structures of the TLPs revealed a high degree of similarity. RcTLP genes were found on all chromosomes except for chromosome four. Cis-regulatory elements (CEs) were identified in the promoters of all RcTLPs, including CEs associated with growth, development and hormone-responsiveness, as well as abiotic and biotic responses, indicating they play diverse roles in rose. Transcriptomics analysis revealed that RcTLPs had tissue-specific expression patterns, and several root-preferential RcTLPs were responsive to drought and salinity stress. Quantitative PCR analysis of six RcTLPs under ABA, PEG and NaCl treatment confirmed the differentially expressed genes identified in the transcriptomics experiment. In addition, silencing RcTLP6 in rose leaves led to decreased tolerance to salinity stress. We also screened proteins which may interact with RcTLP6 to understand its biological roles. This study represents the first report of the TLP gene family in rose and expands the current understanding of the role that RcTLP6 plays in salt tolerance. These findings lay a foundation for future utilization of RcTLPs to improve rose abiotic stress tolerance.

The conversion of flavonoid glycosides and their analogs to their lipophilic ester derivatives was developed by nanobiocatalysts from immobilizing Thermomyces lanuginosus lipase (TLL) on polydopamine-functionalized magnetic Fe3O4 nanoparticles (Fe3O4-PDA-TLL). The behavior investigation revealed that Fe3O4-PDA-TLL exhibits a preference for long chain length fatty acids (i.e., C10 to C14) with higher reaction rates of 12.6–13.9 mM/h. Regarding the substrate specificity, Fe3O4-PDA-TLL showed good substrate spectrum and favorably functionalized the primary OH groups, suggesting that the steric hindrances impeded the secondary or phenolic hydroxyl groups of substrates into the bonding site of the active region of TLL to afford the product.

BURP proteins are unique to plants and may contribute greatly to growth, development, and stress responses of plants. Despite the vital role of BURP proteins, little is known about these proteins in rose (Rosa spp.). In the present study, nine genes belonging to the BURP family in R. chienesis were identified by using multiple bioinformatic approaches against the rose genome database. The nine RcBURPs, with diverse structures, were located on all chromosomes of the rose genome, except for Chr2 and Chr3. Phylogenic analysis revealed that these RcBURPs can be classified into eight subfamilies, including BNM2-like, PG1β-like, USP-like, RD22-like, BURP-V, BURP-VI, BURP-VII, and BURP-VIII. Conserved motif and exon-intron analyses indicated a conserved pattern within the same subfamily. The presumed cis-regulatory elements (CREs) within the promoter region of each RcBURP were analyzed and the results showed that all RcBURPs contained different types of CREs, including abiotic stress-, light response-, phytohormones response-, and plant growth and development-related CREs. Transcriptomic analysis revealed that a BURP-V member, RcBURP4, was induced in rose leaves and roots under mild and severe drought treatments. We then overexpressed RcBURP4 in Arabidopsis and examined its role under abscisic acid (ABA), NaCl, polyethylene glycol (PEG), and drought treatments. Nine stress-responsive genes expression were changed in RcBURP4-overexpressing leaves and roots. Furthermore, RcBURP4-silenced rose plants exhibited decreased tolerance to dehydration. The results obtained from this study provide the first comprehensive overview of RcBURPs and highlight the importance of RcBURP4 in rose plant.

Nine RcBURPs have been identified in Rosa chinensis , and overexpression of RcBURP4 increased ABA, NaCl sensitivity, and drought tolerance in transgenic Arabidopsis . BURP proteins are unique to plants and may contribute greatly to growth, development, and stress responses of plants. Despite the vital role of BURP proteins, little is known about these proteins in rose (Rosa spp.). In the present study, nine genes belonging to the BURP family in R. chinensis were identified using multiple bioinformatic approaches against the rose genome database. The nine RcBURPs, with diverse structures, were located on all chromosomes of the rose genome, except for Chr2 and Chr3. Phylogenic analysis revealed that these RcBURPs can be classified into eight subfamilies, including BNM2-like, PG1β-like, USP-like, RD22-like, BURP-V, BURP-VI, BURP-VII, and BURP-VIII. Conserved motif and exon–intron analyses indicated a conserved pattern within the same subfamily. The presumed cis-regulatory elements (CREs) within the promoter region of each RcBURP were analyzed and the results showed that all RcBURPs contained different types of CREs, including abiotic stress-, light response-, phytohormones response-, and plant growth and development-related CREs. Transcriptomic analysis revealed that a BURP-V member, RcBURP4, was induced in rose leaves and roots under mild and severe drought treatments. We then overexpressed RcBURP4 in Arabidopsis and examined its role under abscisic acid (ABA), NaCl, polyethylene glycol (PEG), and drought treatments. Nine stress-responsive genes expression were changed in RcBURP4-overexpressing leaves and roots. Furthermore, RcBURP4-silenced rose plants exhibited decreased tolerance to dehydration. The results obtained from this study provide the first comprehensive overview of RcBURPs and highlight the importance of RcBURP4 in rose plant.