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Dialogue policy learning (DPL) is a key component in a task-oriented dialogue (TOD) system. Its goal is to decide the next action of the dialogue system, given the dialogue state at each turn based on a learned dialogue policy. Reinforcement learning (RL) is widely used to optimize this dialogue policy. In the learning process, the user is regarded as the environment and the system as the agent. In this paper, we present an overview of the recent advances and challenges in dialogue policy from the perspective of RL. More specifically, we identify the problems and summarize corresponding solutions for RL-based dialogue policy learning. In addition, we provide a comprehensive survey of applying RL to DPL by categorizing recent methods into five basic elements in RL. We believe this survey can shed light on future research in DPL.

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650–900 nm) to NIR-II (900–1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal–organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

Objective. To develop a deep learning-assisted recovery and nursing system after total hip arthroplasty and to conduct clinical trials in order to verify its accuracy. Methods. In our study, based on manual labeling, the human hip X-ray image library was established, and the deep neural network based on Mask R-CNN was built. The labeled medical images were used to train the model, providing reference for nursing decision after hip replacement. A total of 80 patients with hip injury from 2016 to 2019 were selected for the study. In our paper, the patients were divided into experimental group and control group. The pertinence and effectiveness of the model for postoperative care were evaluated by comparing the hip pain (VAS index), recovery (Harris score), self-care ability (Barthel index), and postoperative complication rate between the two groups. Results. The pain and complications in the experimental group were significantly lower than those in the control group, the difference being statistically significant (P<0.05); the recovery of hip joint and self-care ability were higher than those in the control group, the difference being statistically significant (P<0.05); the other differences were not statistically significant (P>0.05). Conclusion. The application of deep learning method in the rapid nursing after total hip replacement can significantly improve the nursing ability. Compared with the traditional method, it has stronger pertinence, faster postoperative recovery, lower incidence of complications, and greatly improves the postoperative quality of life of patients with hip injury.

Endometrial carcinoma (EC) is one of the most common gynecological malignancies. Its incidence rate has been increasing year by year. The prognostic factors and treatment strategies of EC have aroused wide concern. The effects of peritoneal cytology on the prognosis and treatment of EC remain controversial. Some factors, such as differentiation degree, muscle invasion, and tumor size, are related to positive peritoneal cytology. Hysteroscopy is commonly used in the diagnosis and treatment of endometrial cancer, but hysteroscopic surgery may cause the tumor to spread into the abdominal cavity, resulting in positive peritoneal cytology. In this review, we discuss the factors related to positive peritoneal cytology and the influence of positive peritoneal cytology on the prognosis of endometrial cancer. Suspicious positive peritoneal cytology may be an independent risk factor for endometrial cancer. The positive rate of peritoneal tumor cells in type II endometrial cancer is higher than other cells and is an independent risk factor for type II endometrial cancer. We also discuss the effects of peritoneal cytology on treatment decisions. Aggressive treatments seem to be more beneficial for patients with positive ascites cytology, but there is a lack of large-scale prospective clinical studies on their effectiveness and safety. The application of peritoneal cytology for endometrial cancer has been decreased in recent years. We believe that peritoneal cytology is necessary for this type of cancer. However, more studies on peritoneal cytology in endometrial cancer should be carried out.

This study provides a comprehensive, comparative and updated estimates of temporal patterns of lower respiratory infections (LRIs) globally over the past three decades.The data on morbidity and mortality of patients with LRIs at the global, regional and national levels were retrieved from the Global Burden of Disease (GBD) 2019 study.Globally, the incident cases of LRIs increased from 414,342,866 [95% uncertainty interval (UI):383,529,625 to 449, 086,938]in 1990 to 488,902,504(95% UI: 457,572,987 to 522,635,542)in 2019 with the age standardized incidence rate (ASIR) decreased from 8,276/100,000 persons (95% UI: 7,727 to 8,892) to 6,295/100,000 persons (95% UI: 5,887 to 6,737) between 1990 and 2019. Number of LRIs deaths were 2,493,200 (95% UI: 2,268,184 to 2,736,184) in 2019, a decrease of 24.9% (95% UI: -34.4 to -15.4) in the past 30 years. Meanwhile, the age-standardized death rate (ASDR) declined also from 67/100,000 persons (95% UI: 61 to 73) in 1990 to 34/100,000 persons (95% UI: 31 to 38) in 2019. Moreover, the numbers and age-standardized rates per 100,000 persons of morbidity and mortality varied widely by age, sex, Socio-Demographic Index (SDI) quintiles, and geographical locations in 2019.LRIs remain a major public health concern . Some differences in age, sex, SDI quintiles, and geographical locations contribute to LRIs-related global health policy development and health system resource optimization.

Objective. Acute lung injury (ALI) is a life-threatening complication during sepsis and contributes to multiple organ failure and high mortality for septic patients. The present study aims to investigate the role and molecular basis of growth differentiation factor 7 (GDF7) in sepsis-induced ALI. Methods. Mice were subcutaneously injected with recombinant mouse GDF7 Protein (rmGDF7) and then intratracheally injected with lipopolysaccharide (LPS) to generate sepsis-induced ALI. Primary peritoneal macrophages were isolated to further evaluate the role and underlying mechanism of GDF7 in vitro. Results. GDF7 was downregulated in LPS-stimulated lung tissues, and rmGDF7 treatment significantly inhibited inflammation and oxidative stress in ALI mice, thereby preventing LPS-induced pulmonary injury and dysfunction. Mechanistically, we found that rmGDF7 activated AMP-activated protein kinase (AMPK), and AMPK inhibition significantly blocked the anti-inflammatory and antioxidant effects of rmGDF7 during LPS-induced ALI. Further findings revealed that rmGDF7 activated AMPK through a downregulated stimulator of interferon gene (STING) in vivo and in vitro. Conclusion. GDF7 prevents LPS-induced inflammatory response, oxidative stress, and ALI by regulating the STING/AMPK pathway. Our findings for the first time identify GDF7 as a potential agent for the treatment of sepsis-induced ALI.

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.

Despite their high theoretical energy density, the application of lithium-sulfur batteries is seriously hindered by the polysulfide shuttle and sluggish kinetics, especially with high sulfur loading and under low electrolyte usage. Herein, to facilitate the conversion of lithium polysulfides, nickel-boron (Ni-B) alloy nanoparticles, dispersed uniformly on carbon nanotube microspheres (CNTMs), are used as sulfur hosts for lithium-sulfur batteries. It is demonstrated that Ni-B alloy nanoparticles can not only anchor polysulfides through Ni-S and B-S interactions but also exhibit high electrocatalytic capability toward the conversion of intermediate polysulfide species. In addition, the intertwined CNT microspheres provide an additional conductive scaffold in response to the fast electrochemical redox. The enhanced redox kinetics is beneficial to improve the specific capacity and cycling stability of the sulfur cathode, based on the fast conversion of lithium polysulfides and effective deposition of the final sulfide products. Conclusively, the S/Ni-B/CNTM composite delivers a high specific capacity (1112.7 mAh gs-1) along with good cycle performance under both high sulfur loading (8.3 mg cm-2) and a lean electrolyte (3 μL mgs-1). Consequently, this study opens up a path to design new sulfur hosts toward lithium-sulfur batteries.

MicroRNA‐24‐3p (miR‐24‐3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer‐associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF‐derived exosomal miR‐24‐3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF‐derived exosomal miR‐24‐3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR‐24‐3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR‐24‐3p was verified using ChIP and dual‐luciferase reporter gene assays. Exosomes were isolated from miR‐24‐3p inhibitor–treated CAFs (CAFs‐exo/miR‐24‐3p inhibitor), which were used in combination with gain‐of‐function and loss‐of‐function experiments and MTX treatment. CCK‐8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR‐24‐3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR‐24‐3p and could up‐regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down‐regulated miR‐24‐3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR‐24‐3p was transferred into CC cells via CAF‐derived exosomes. CAF‐derived exosomal miR‐24‐3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF‐derived exosomal miR‐24‐3p accelerated resistance of CC cells to MTX by down‐regulating CDX2/HEPH axis.

Objective To investigate the risk factors for Adverse pregnancy outcome (APOs) in patients with new-onset SLE during pregnancy. Methods Eighty-five patients with new-onset SLE during pregnancy were analyzed retrospectively. Univariate and multivariate logistic regression were used to identify risk factors for different APOs (pregnancy loss, preterm birth, fetal growth restriction, and eclampsia/preeclampsia). A two-sided p-value below 0.05 was considered significant, and two-sided 95% confidence intervals (CIs) are reported. Results Multivariate analysis indicated that renal involvement (aOR: 7.356; 95%CI:1.516,35.692) and greater SLE disease activity index (SLEDAI) grade (aOR:5.947;95%CI: 1.586,22.294) increased the risk for composite APO, and that use of heparin therapy (aOR: 0.081; 95%CI: 0.012, 0.532) was a protective factor. Advanced gestational age at disease onset (aOR: 0.879; 95%CI: 0.819,0.943) and high serum albumin level (aOR: 0.908,95%CI: 0.831,0.992) protected against pregnancy loss. Renal involvement increased the risk for preterm birth (aOR: 2.272; 95%CI: 1.030,7.222) and fetal growth restriction (aOR: 9.070; 95%CI: 1.131,72.743). Hypertension (aOR: 19.185; 95%CI: 3.921,93.868), renal involvement (aOR: 8.380, 95%CI: 1.944,74.376) increased the risk for eclampsia/preeclampsia. Conclusion New onset SLE during pregnancy increased the risk for multiple APOs. Timely management of the risk factors identified here may help to improve pregnancy outcomes in these patients.

The design and utilization of dual sites for synergistic catalysts has been recognised as an efficient method towards high-efficiency catalysis in the cyanosilylation of aldehydes, which gives key intermediates for the synthesis of a number of valuable natural and pharmaceutical compounds. However, most of the reported dual-site catalysts for this reaction were homogeneous, accompanied by potential deactivation through internal complexation of the dual sites. Herein, by the rational selection of an uncoordinated tertiary nitrogen based tricarboxylic ligand (tris[(4-carboxyl)-phenylduryl]amine, H3TCBPA), a new three-dimensional calcium-based metal-organic framework (MOF), Ca3(TCBPA)2(DMA)2(H2O)2 (1, where TCBPA = ionized tris[(4-carboxyl)-phenylduryl]amine and DMA = N,N-dimethylacetamide), possessing accessible dual catalytic sites, Lewis-basic N and Lewis-acidic Ca, has been designed and constructed by a one-pot solvothermal reaction. As expected, 1 is capable of dually and heterogeneously catalysing the cyanosilylation of aldehydes at room temperature, and can be reused for at least 6 runs with a maximum turnover number (TON) of 1301, which is superior to most reported cases. Additionally, 1 shows CO2 adsorption ability and conversion with epoxides, which is beneficial for the establishment of a sustainable society.

Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr

Challenges encountered in plant metabolites characterization by liquid chromatography/mass spectrometry can arise from the insufficient chromatography separation, the lack of specific database, and low reliability of identification because of the ubiquitous isomerism. Herein, we present an integral approach, by combining comprehensive off-line two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), automatic peak annotation, molecular networking, and collision cross section (CCS) prediction, aimed to improve the resolution and reliability in MS-oriented metabolites characterization. Using the seeds of Cuscuta chinensis as a case, the configuration of an XBridge Amide column of hydrophilic interaction chromatography (HILIC) and a Zorbax SB-Aq column of reversed-phase chromatography (RPC), in an off-line mode, showed the orthogonality of 0.73 and effective peak capacity of 4361. Data-independent high-definition MS

To systematically evaluate the whole-transcriptome sequencing data of cholangiocarcinoma (CHOL) to gain more insights into the transcriptomic landscape and molecular mechanism of this cancer, we performed whole-transcriptome sequencing based on the tumorous (C) and their corresponding non-tumorous adjacent to the tumors (CP) from eight CHOL patients. Subsequently, differential expression analysis was performed on the C and CP groups, followed by functional interaction prediction analysis to investigate gene-regulatory circuits in CHOL. In addition, The Cancer Genome Atlas (TCGA) for CHOL data was used to validate the results. In total, 2,895 differentially expressed messenger RNAs (dif-mRNAs), 56 differentially expressed microRNAs (dif-miRNAs), 151 differentially expressed long non-coding RNAs (dif-lncRNAs), and 110 differentially expressed circular RNAs (dif-circRNAs) were found in CHOL samples compared with controls. Enrichment analysis on those differentially expressed genes (DEGs) related to miRNA, lncRNA, and circRNA also identified the function of spliceosome. The downregulated hsa-miR-144-3p were significantly enriched in the competing endogenous RNA (ceRNA) complex network, which also included 7 upregulated and 13 downregulated circRNAs, 7 upregulated lncRNAs, and 90 upregulated and 40 downregulated mRNAs. Moreover, most of the DEGs and a few of the miRNAs (such as hsa-miR-144-3p) were successfully validated by TCGA data. The genes involved in RNA splicing and protein degradation processes and miR-144-3p may play fundamental roles in the pathogenesis of CHOL., Graphical Abstract, The whole-transcriptome sequencing data of cholangiocarcinoma (CHOL) were systematically evaluated to gain more insights into the transcriptomic landscape and molecular mechanism of this cancer.

Development of ultra-sensitive and high specific aptasensors is important for early diagnosis of prostate cancer. Herein, ultrasensitive detection of prostate specific antigen (PSA) aptasensor was realized based on the “on-off-on” model via fluorescence (FL) covalent energy transfer between g-C3N4 quantum dot (g-CNQDs) and palladium triangular plates (Pd TPs). Specifically, the Pd TPs were primarily linked with PSA aptamer (PA) as the reporter probe, followed by attaching them onto the g-CNQDs surfaces, causing the highly enlarged FL quenching rate (ca. 75%). After the introduction of PSA, the FL intensities recovered again because of the distinctively stronger affinity of PA to PSA than that of g-CNQDs. The bond of pyridine N with Pd was identified as efficient energy transfer pathway through the X-ray photoelectron spectroscopy (XPS) and FL measurements. The surface plasmon resonance (SPR) experiments certified the remarkably different affinity of PA towards g-CNQDs and PSA. The as-constructed FL aptasensor can accurately quantify PSA with wide linear range of 10 pg mL−1-50 ng mL−1 and ultra-low limit of detection (LOD, 4.2 pg mL−1), indicating the promising applications in clinical assay and biological detection.

A biomimetic assembly of per-O-methylated-cyclodextrin dimer with cobalt proto-porphyrin (CoIII-PPIX@Py2CD) was achieved via covalent linkage between CoIII of CoIII-PPIX and pyridine N of Py2CD (primarily synthesized by the acyl chlorination reaction of two β-CDs monomers with 3,5-bis (bromomethyl) pyridine). Ultraviolet–visible (UV–vis) and circular dichroism (CD) absorption spectroscopy, and NMR hydrogen spectroscopy (H1-NMR) were adopted to carefully characterize the structure of Py2CD and its functional assembly with CoIII-PPIX. X-ray photoelectron spectroscopy (XPS) was employed to affirm the binding of the as-obtained CoIII-PPIX@Py2CD, whose electrochemical kinetics were extensively studied to validate the feasibility in the catalytic reduction of hydrogen peroxide (H2O2). The developed sensor displayed the wide linear range for H2O2 detection and the low detection limit of 2.47 × 10−7 M. This work sheds some constructive lights on rational design and synthesis of preeminently biomimic carrier and high cost-effectiveness catalyst for (bio)analytical applications.

Quasitopological electromagnetism has an important influence on the strong gravity of dyonic black hole. For example three photon spheres with one being stable are found and we wish to test them with the observed black hole shadow. We are primarily concerned with the thermodynamics and phase transition for a dyonic anti-de Sitter (AdS) black hole when the quasitopological electromagnetism is included.Unlike in a black hole solution without quasitopological electromagnetism, we observe a triple point phase structure by varying the coupling parameters. Of particular interest, for certain parameter values, two separate coexistence curves are present, which is an additional novel phase structure that is absent in a black hole solution without quasitopological electromagnetism. The critical exponents share the same values as mean field theory. These results uncover the intriguing properties of dyonic AdS black holes with quasitopological electromagnetism from a thermodynamic point of view., Comment: 18 pages, 11 figures and 2 tables. Major revision

Refill friction stir spot welding, also known as friction spot welding (FSpW), is a solid-state welding process suitable for spot joining of lightweight materials. Through the efforts of improving joint quality for similar and dissimilar materials, for example, aluminum and magnesium, this joining technology is well developed. The joining mechanism and process characteristics of FSpW have been widely studied. However, the application of FSpW in industry has not been entirely successful. In this review article, the research of similar and dissimilar material joints, such as, Al/Cu, Al/Ti, Al/Mg and Al/Steel, is summarized. The microstructural features and mechanical properties of the joints, welding tool and the application development are discussed in detail.

In Einstein-{\AE}ther theory, the Lorentz symmetry is locally broken in the high-energy regime due to the presence of the{\AE}ther field. This shall leave significant imprint on astronomical observation. In this paper, we investigate the optical appearance of two types of the static and spherically symmetric black holes in Einstein-{\AE}ther theory. Via Euler-Lagrange equation, we obtain the equations of motion of the photon and calculate the total deflection angle of the photon trajectory around the black hole. By classifying the light rays with the total number of orbits, we study the effects of coupling constants on the direct image, lensing ring, and photon ring. The features of the light trajectories are also investigated by comparing with the Einstein-{\AE}ther theory and general relativity. Moreover, we also show the explicit optical appearance of black holes surrounded by thin disk emissions with three characteristic emitted models. The results indicate that the direct image gives the main contribution to the total flux, and the lensing ring just gives a very small contribution, whereas the role of the photon ring is negligible. The optical appearances are also found to significantly rely on these coupling constants., Comment: 19 pages, 6 figures

We explored the seasonal dynamics and climate responses of radial variation of Chinese fir, we continuously monitored intra-annual stem radial size changes with the automated dendrometers in central Jiangxi Province in 2016 and 2017. We analyzed daily and seasonal dynamics of radial variations, and their Spearman correlations with climatic factors. We found that the diurnal radial variations had a pattern of contraction during the day and expansion at night. The growth onset in 2017 was one month earlier than that in 2016, whereas the continuous tree water deficit in the dry season caused the cessation one month early. During the main growing season (from April to September), the radial increment was significantly positively correlated with precipitation and relative humidity but negatively correlated with photosynthetically active radiation and vapor pressure deficit in both wet and dry seasons. However, the correlation for tree water deficit was opposite to stem radial increment. Severe water deficit significantly enhanced the impacts of soil water content on stem radial variation in the dry season. Moisture condition was always the key factor affecting stem radial variation of Chinese fir. Appropriate measures such as increasing soil water content could promote stem radial growth during summer drought.为探讨杉木径向变化的季节动态及其气候响应特征,利用径向生长仪连续2年(2016—2017年)监测了江西中部杉木的径向变化过程,分析了径向变化的日动态、季节动态规律及其与气候因子的相关性。结果表明: 杉木日径向昼夜变化呈白天收缩、夜间膨胀的格局;2017年径向生长开始时间比2016年提前一个月,但旱季持续的水分亏缺使生长季也早一个月结束;在主要生长季内(4—9月),无论湿季与旱季,径向增长量与降雨、相对湿度呈显著正相关,与光合有效辐射、饱和水汽压差呈显著负相关,而水分亏缺量的气候相关性与径向增长量相反;旱季严重缺水时土壤含水量对径向变化的影响显著增强。水分条件始终是影响杉木径向变化的关键因素,夏季干旱时可通过提高土壤含水量等有效途径促进杉木径向生长。.

Background Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. Methods Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. Results LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. Conclusion Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

OBJECTIVE: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.

We measured the activities of six kinds of enzyme, including β-glucosidase (BG), β-N-acetyl-glucosaminidase (NAG), leucine aminopeptidase (LAP), acid phosphatase (AP), polyphenol oxidase (POX), peroxidase (POD), as well as enzyme stoichiometric ratios and soil physical and chemical properties at 0-10 and 10-20 cm layers across typical Pinus massoniana plantation, Pinus elliottii plantation and mixed plantation of P. massoniana and Schima superba (broadleaved-conifer mixed plantation) in mid-subtropical China. Key factors driving the variation in soil enzyme activity and stoichiometry among different stand types were investigated. The results showed that the activities of soil BG and LAP were significantly affected by stand type. Soil BG activity at 10-20 cm soil layer was significantly higher in P. elliottii plantation than in P. massoniana plantation, while the activity of LAP was highest in the P. massoniana plantation. Soil BG/(NAG+LAP) and BG/AP at 10-20 cm layer of P. elliottii plantation were significantly higher than those of P. massoniana plantation, while (NAG+LAP)/AP of P. massoniana plantation was significantly higher than those of P. elliottii plantation and mixed plantation. The vector length of enzyme stoichiometry at 10-20 cm soil layer was significantly different among stand type, with an order of P. elliottii plantationbroadleaved-conifer mixed plantationP. massoniana. The vector angles of enzyme stoichiometry in the three plantations were greater than 45°, with the vector angle in the P. elliottii plantation at 10-20 cm soil layer being significantly greater than that of the P. massoniana plantation. Results from redundancy analysis showed that soil carbon quality index and the ratio of soil organic carbon to total phosphorus (C/P), soil water content and C/P were the key factors affecting soil enzyme activity and stoichiometry at 0-10 and 10-20 cm soil layers, respectively. The quantity and quality of soil carbon and phosphorus, and soil water content played a key role in regulating nutrient cycling in mid-subtropical plantation ecosystem.以中亚热带典型的马尾松林、湿地松林和马尾松-木荷混交林(针阔混交林)为研究对象,分析不同林分类型下0～10和10～20 cm土层的β-D-葡萄糖苷酶(BG)、β-N-乙酰氨基葡萄糖苷酶(NAG)、亮氨酸氨基肽酶(LAP)、酸性磷酸酶(AP)、多酚氧化酶(POX)、过氧化物酶(POD)6种土壤酶活性,以及酶化学计量比及土壤理化性质特征,分析驱动中亚热带典型林分类型土壤酶活性及其计量比变异的主要因素。结果表明: 林分类型显著影响了土壤BG和LAP活性,表现为湿地松林10～20 cm土层土壤BG显著高于马尾松林,而LAP在马尾松林最高;湿地松林10～20 cm土层土壤BG/(NAG+LAP)、BG/AP显著高于马尾松林,而马尾松林(NAG+LAP)/AP显著高于湿地松林和针阔混交林;林分类型间酶化学计量的向量长度在10～20 cm土层差异显著,表现为湿地松林针阔混交林马尾松林。3种人工林酶化学计量的向量角度均大于45°,其中在湿地松林10～20 cm土层向量角度显著大于马尾松林。冗余分析表明,土壤碳质量指数和有机碳与全磷的比值(C/P)以及土壤含水量和C/P分别是0～10和10～20 cm土层土壤酶活性及其化学计量的关键影响因素,土壤碳和磷的数量和质量,以及土壤含水量在调节中亚热带人工林生态系统养分循环中发挥关键作用。.

Background To investigate the role of plasma metanephrines (MN) and normetanephrines (NMN), in predicting cardiovascular events in essential hypertensive patients. Methods This was a retrospective analysis of 688 hospitalized patients diagnosed with essential hypertension at the Beijing Anzhen hospital from October 2016 to August 2018, with a median (interquartile range) follow-up time of 24 (20–29) months. The primary endpoint was defined as all-cause death and/or readmission for cardiovascular or cerebrovascular events. Patients were divided into event (n = 57) and nonevent (n = 631) groups. High-performance liquid chromatography–tandem mass spectrometry was used to determine plasma MN and NMN levels. According to the cutoff value of plasma NMN from receiver operating characteristic analysis, patients were further divided into NMN ≤125.75 ng/l and NMN >125.75 ng/l groups. The effects of NMN on the prognosis of hypertensive patients were evaluated using Kaplan–Meier curves and multivariate Cox regression analysis. Results The plasma NMN levels of the event group were higher than those of the nonevent group [110.0 (74.0–135.0) vs. 88.5 (62.0–119.5) ng/l, P = 0.004]. The incidence of the primary endpoint event in NMN ≤125.75 ng/l and NMN >125.75 ng/l groups was 6.0% and 15.8%, respectively. Kaplan–Meier analysis showed that patients with higher baseline NMN levels were more likely to experience adverse events (P < 0.001). Cox regression analysis showed that patients in NMN >125.75 ng/l group had over twofold higher risk of the primary endpoint event than those in NMN ≤125.75 ng/l group (HR = 2.11, 95% CI 1.15–3.84, P = 0.015). Conclusions Elevated plasma NMN levels are associated with higher risk of cardiovascular and cerebrovascular events in patients with essential hypertension.

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

In this study, indoor simulation experiments were performed to elucidate the effects of migration and transformation of dissolving organic matter (DOM) during the decay of algal blooms. Based on ultraviolet-visible spectra (UV-vis) and excitation-emission matrix spectroscopy (EEMs), spectral characterizations of dissolved organic matter (DOM) in overlying water were evaluated with analyses of the physical and chemical indexes, variation in dissolved organic carbon (DOC), and variation in dissolved inorganic carbon (DIC). Results showed that at the early stage of decay, a large amount of organic matter was released, and dissolved oxygen (DO) decreased sharply. With the extension of reaction time, DOC gradually changed into DIC, which further changed the oxidation-reduction and acid-base characteristics of the water. UV-vis spectra showed that a large amount of DOM was released with high aromaticity and a high degree of humification, and the released DOM was gradually degraded. With the application of parallel factor analysis in excitation-emission matrix spectroscopy (EEM-PARAFAC), three fluorescence components were analyzed:refractory humic-like substances (C1), protein-like tryptophan substances (C2) produced by algae, and fulvic-like substances (C3) related to microbial activities. Most protein-like tryptophan substances were degraded into fulvic-like substances by microorganisms during the decaying process. Heterotrophic microorganisms promoted the release of algae-derived DOM and accelerated the degradation of DOM. The DOM born during algae blooms decaying process was eventually converted into humic-like substance, which was difficult to be degraded. We analyzed correlations of water quality, UV-vis spectrum, and EEMs parameters. Results showed that ORP was positively correlated (

Cancer accounted for 16% of all death worldwide in 2018. Significant progress has been made in understanding tumor occurrence, progression, diagnosis, treatment, and prognosis at the molecular level. However, genomics changes cannot truly reflect the state of protein activity in the body due to the poor correlation between genes and proteins. Quantitative proteomics, capable of quantifying the relatively different protein abundance in cancer patients, has been increasingly adopted in cancer research. Quantitative proteomics has great application potentials, including cancer diagnosis, personalized therapeutic drug selection, real-time therapeutic effects and toxicity evaluation, prognosis and drug resistance evaluation, and new therapeutic target discovery. In this review, the development, testing samples, and detection methods of quantitative proteomics are introduced. The biomarkers identified by quantitative proteomics for clinical diagnosis, prognosis, and drug resistance are reviewed. The challenges and prospects of quantitative proteomics for personalized medicine are also discussed., Graphical abstract, Yang et al. introduce the development, samples tested, and detection methods of quantitative proteomics. Biomarkers for clinical diagnosis, prognosis, and drug resistance identified by quantitative proteomics are reviewed. The challenges and prospects of quantitative proteomics for personalized medicine are also discussed.

In recent years, network representation learning has attracted extensive attention in the academic field due to its significant application potential. However, most of the methods cannot explore edge information in the network deeply, resulting in poor performance at downstream tasks such as classification, clustering and link prediction. In order to solve this problem, we propose a novel way to extract network information. First, the original network is transformed into an edge network with structure and edge information. Then, edge representation vectors can be obtained directly by using an existing network representation model with edge network as its input. Node representation vectors can also be obtained by utilizing the relationships between edges and nodes. Compared with the structure of original network, the edge network is denser, which can help solving the problems caused by sparseness. Extensive experiments on several real-world networks demonstrate that edge network outperforms original network in various graph mining tasks, i.e., node classification and node clustering.

Six series of 4-(benzo[c][1,2,5]thiadiazol-5-yl)-3(5)-(6-methylpyridin-2-yl)- pyrazoles 18a–d, 19a–d, 22a–d and 3(5)-(6-methylpyridin-2-yl)-4-(thieno[3,2,-c]- pyridin-2-yl)pyrazoles 20a–d, 21a–d, 23c, 23d have been synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activities in enzymatic assays. Among these compounds, the most active compound, 22c, inhibited ALK5 phosphorylation with an IC50 value of 0.030 μM in the enzymatic assay. Compound 22c showed four-fold more potent activity against ALK5 kinase than the clinical candidate, compound LY-2157299. The selectivity index of 22c against p38α MAP kinase is 235, which is much higher than that of LY-2157299 (4) and equally selective to that of EW-7197 (218). Compound 22c effectively suppressed protein and mRNA expression of collagen I and α-SMA in TGF-β-induced LX-2 human hepatic stellate cell (HSC), this result shows that compound 22c has the ability to inhibit the activation of HSC. Compound 22c is expected to be a preclinical candidate for the treatment of hepatic fibrosis.

Zinc ions (Zn2+) act as a transcription factor in eukaryotic cells for mediating protein-protein interactions in human healthy. The simple and sensitive detection of Zn2+ is the crucial mission in analytical field. This work demonstrated a novel and fast Zn2+ detection strategy based on “signal on” mode with electrochemiluminescence (ECL) luminophore, in which singlet oxygen was generated via electrocatalytic reduction of zinc proto-porphyrin IX grafted onto Pd nanocubes (ZnPPIX-Pd NCs). In protocol, Pd NCs were synthetized under hydrothermal conditions and aminated through thermal oxidative polymerization of 3-aminopropyltriethoxysilane (APTES), followed by further linking with PPIX via amide reaction. The resulting PPIX-Pd NCs effectively captured Zn2+ in chelation and monitored by Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-vis) absorption spectroscopy. By virtue of the metal resonance responses of Pd NCs, an intense monochromic, potential shuffling and enhanced ECL irradiation shows up for the hybrid nanocomposite with H2O2 as the coreactant. To this end, an ultrasensitive method based on the nanocomposite with a “signal-on” model was developed for Zn2+ detection with a low detection limit down to 0.38 nM (based on a S/N= 3), excellent precision and high stability. The ECL strategy reveals the potential application in molecular diagnosis and offers a new avenue for bioassay of structural Zn(II) proteins and zinc finger-binding nucleotides.

Aptamer-based bioassay of biomarker has broad applications in clinical research and disease diagnosis. In this work, a label-free aptamer biosensor for ultrasensitive thrombin (TB) detection was constructed based on highly enhanced electrochemiluminescence (ECL) of functional palladium nanocones (Pd NCs) with tripropylamine (TPA) system. Herein, well-defined Pd NCs were initially functionalized by mercaptoethanol (MCH) as an ECL emitter and immobilized onto the glassy carbon electrode (GCE) initially grafted with amine-terminated polyamidoamine (PAMAM) via electro-oxidation reaction. Under optimal conditions, the ECL intensity of the Pd NCs/TPA system was about 2.5 times enhancement when compared to that of bare GCE. The ECL and cyclic voltammetry (CV) were synchronously employed to illustrate the enhanced ECL mechanism. By virtue of the linkage of the modified Pd NCs with specified TB aptamer (TBA) containing sulfydryl group, a label-free ECL detection platform was designed. After full coverage of the nonspecific sites with bovine serum albumin (BSA), an ECL biosensor for TB detection was constructed by taking the advantage of the steric hindrance effects, showing the wider linear range, lower detection limit of TB (even down to 6.76 fM), superb selectivity and stability. The current strategy provides a highly sensitive platform for detection of various biomolecules in bioanalysis.

Three series of ursolic acid derivatives containing an aminoguanidine moiety were designed, synthesized, and evaluated for anti-bacterial and anti-inflammatory activity. Some compounds displayed potent anti-bacterial activity against Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains, with minimum inhibitory concentration (MIC) values in the range of 2–64 µg/mL. Compounds 3a, 5a, and 7l showed significant inhibitory activity against the Gram-positive bacterial strain Staphylococcus aureus RN 4220, the Gram-negative bacterial strain Escherichia coli 1924, and four multidrug-resistant Gram-positive bacterial strains, with MIC values of 2 and 4 µg/mL. In anti-inflammatory tests, most of the compounds exhibited potent activity, in particular compound 3a displayed the most potent activity with 81.61% inhibition after intraperitoneal administration, which was more potent than ursolic acid and the reference drugs (ibuprofen and indomethacin). The cytotoxic activity of compound 3a was assessed in HeLa, Hep3B, and A549 cells.

Physical elasticity is a major mechanical property of several tissue types, and enormous efforts have been invested into the development of elastomeric biomaterials that mimic properties of native tissue. In the present study, a polycaprolactone-polylactic acid scaffold was photografted with polyacrylamide, tumor necrosis factor-alpha, and insulin-like growth factor 1 to construct a novel scaffold, which was named the polycaprolactone-polylactic acid-polypropylene amine-insulin-like growth factor 1/tumor necrosis factor-α (PCL-PLA-PAAm-IGF-1/TNF-α) scaffold. Its inhibitory effect on cell senescence of bone marrow mesenchymal stem cells was studied. When the PCL-PLA-PAAm-IGF-1/TNF-α scaffolds were transplanted into a rat model of acute hepatic failure, we found that the scaffolds clearly contributed to liver repair. The simple method presented here may be useful for the preparation of cell-scaffold complexes for liver tissue engineering.

Electrochemiluminescence (ECL) has attracted significant interest because of its superior properties and potential applications in bioanalysis, and therefore many luminescent nanomaterials have been developed. Herein, well-defined Pd nanocones (Pd NCs) were facilely obtained by a one-pot hydrothermal method with poly- l -lysine (PLL) as a green protecting ligand, which were mainly characterized by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Then, the as-obtained Pd NCs were first explored as an anodic ECL emitter, where tripropylamine (TPA) worked as the coreactant to boost the ECL emission. The possible ECL mechanism of Pd NCs/TPA system was extensively explored by ECL and electrochemical techniques. Briefly, the ECL emission underwent the oxidation-reduction route, in which both Pd NCs and TPA were initially oxidized, and then the oxidized TPA lost an proton to form reducing agent (TPA·) strongly reacted with the oxidized Pd NCs generating Pd NCs* for the emission. Furthermore, using dopamine (DA) as an ECL quencher, an ultrasensitive sensor was constructed for DA detection. The fabricated ECL sensor shows high sensitivity and selectivity, good stability, and wide linear range with the low detection limit of 0.46 pM. It offers a new avenue to exploit ECL illuminant and enriches the ECL emission theory.

The basic problems of the low dissolution rate of Tanshinone IIA (TSN) and the instability and precipitation of sodium tanshinone IIA sulfonate (STS) injection limit their usage in clinical. For these facts, the study aims to improve the dissolution rate of TSN and to enhance the sustained release effects of TSN and STS by using SBA-15 mesoporous molecular sieve as a drug carrier. Furthermore, controlling the pore size of SBA-15 and using different loaded methods to achieve expectations and provide a novel scheme for existing Danshen formulations. The effect of loading methods on drug loading efficiency (DL%), as well as the influence of the pore size of SBA-15s, the drug polarities and release mediums on drug loading and release behaviors were analyzed. It was found that the DL% was enhanced with the enlargement of the pore size, and was higher of TSN than STS. The in vitro tests of drug-loaded SBA-15s confirmed that the dissolution rate of TSN was improved obviously as compared with pure TSN. Moreover, SBA-15s prolonged the release times up to 12 h of TSN and 60 h of STS and promoted the sustained-release behaviors by decreasing the pore size. To ascertain the kinetic mechanisms of these samples, the Korsmeyer-Peppas release model was employed and the fitted results indicated that TSN/SBA-15s followed Fickian diffusion and non-Fickian transport was the predominant kinetic release mechanisms for STS/SBA-15s.

Lung is one of important organs and lung diseases seriously affect the health of human beings. In this study, chitosan and gelatin as natural biological macromolecules raw material for the synthesis of ordered colloidal crystal scaffolds (CCS), Fe3O4 magnetic nanoparticles (MNPs) were used as pore-making for the first time. The pore-making agent were added into the hydrogels to synthesis the ordered (magnetic field) and disordered (no magnetic field) CCS. Collagen and basic fibroblast growth factor (bFGF) modified on the surface of CCS. Then mouse lung epithelial cells (TC-1) and normal human bronchial epithelial cells (Beas-2B) were cultured on the scaffold, obviously induced cell proliferation. Various physical and chemical characteristics indicate that the preparation of scaffolds and modified growth factors can greatly promote the proliferation of these two cells. In addition, the scafolld was implanted into the SD rat in vivo, and routine blood tests showed that the stent had a small inflammatory response to the rat. This may be one of the effective strategies for the future treatment of lung injury repair.