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TLR7/8 agonists are immunomodulators for treating skin cancer or virus infections. miR-1258 can activate TLR7/8. This study aims to explore the role of TLR7/8 agonists and miR-1258 in activating liver cancer NK cells. NK cells and DC cells were treated with TLR7/8 agonists R837, ssRNA40 and miR-1258 followed by analysis of hepatocellular carcinoma (HCC) cell behaviors in vivo and in vitro. TLR7/8 agonist miR-1258 activated NKs and promoted DCs maturation. In addition, DCs also assisted NKs to function and enhance the anti-HCC immune responses. The interaction of DCs with NK cells stimulated by TLR7/8 agonist miR-1258 can significantly inhibit tumor development and metastasis in mice HCC model. TLR7 or TLR8 agonists, especially miR-1258, promoted DCs-NKs interaction by promoting the secretion of related cytokines and cell/cell contact, which increased anti-tumor activity of NKs and promoted DC-NK cells to inhibit the growth of HCC cells. In conclusion, miR-1258 simultaneously stimulates the expression of TLR7/8, and promotes NK-DC cells to inhibit the growth of HCC cells, providing a theoretical basis for the treatment of liver cancer.

Lipid raft is a microdomain being rich in cholesterol and sphingolipid and closely related to neurodegenerative diseases such as Alzheimer’s disease and prion disease. Hence the study on the physiological mechanism of lipid raft is helpful to reveal its biological role and its correlations with diseases. Two-photon fluorescence probe for lipid raft is a sharp tool to achieve this goal. A dicyanocarbazolylstilbene-derived two-photon fluorescence probe for lipid raft (DLR) was developed. Both DLR and lipid raft belong to D-π-A (donor-π-acceptor; π: C = C) type rigid planar molecule, and contain four fused carbon rings (one five-membered ring and three six-membered ring), and bear a long carbon chain (C8H17). The excellent comparability between the rigid plane of the probe molecule and the rigid lipid raft could significantly enhance the specific affinity to lipid rafts. DLR’s maximum emission wavelength increased with medium polarity while its fluorescence intensity (FI) augmented with viscosity, and FI in DPPC (dipalmitoylphosphatidylcholine) was 20 times higher than that in DOPC (dioleoylphosphatidylcholine). DLR’s fluorescence lifetime in DPPC was more than 2.2 times longer than that in DOPC. These indicate that DLR can distinguish DPPC from DOPC. Φδs of DLR in DPPC and DOPC were 1350 GM and 67 GM, respectively. DLR can image lipid raft distribution in cells and tissues.

Recent studies have shown that rutin (Quercetin-3-O-rhamnosylglucoside) may have an inhibitory effect on COVID-19. Rutin can be extracted from Tartary buckwheat as an active pharmaceutical ingredient. Nevertheless, its purification is mainly hindered by Kaempferol-3-O-rutinoside (K3R) due to their similar molecular structures. This study intends to propose a simulated moving bed (SMB) chromatography process of rutin and K3R to achieve continuous production. True moving bed (TMB) and SMB models were established to numerically analyze and optimize this process. The system consists of a four-zone SMB with two columns in each zone. The effects of the switch interval, feed flowrate, desorbent flowrate, extract flowrate, raffinate flowrate, and recycle flowrate on the purity and yield of rutin and K3R were investigated and the optimized conditions were chosen as 5 min, 3.5, 40, 34, 9.5, and 24.5 L/min, respectively. Consequently, the purities of 99.64% and 99.25%, and the yields of 99.81% and 99.37% for rutin and K3R were obtained, respectively. The simulation results can provide a guidance for the future industrial application of SF-SMB to separate rutin and K3R.

Based on the prevalence of combined antibiotics and heavy metals contamination in the aquatic environment, this study utilized a microbial approach to achieve simultaneous removal of nitrate (NO

The removal of nitrate (NO

In recent years, under the condition of lack of carbon source, the presence of composite micro-pollutants make the removal of nitrate seriously damaged, and to find a suitable way to solve this problem is imminent. A fixed-biofilm carrier modified by mixing sponge iron (SI) and kapok fiber (KF) combined with strain Zoogloea sp. FY6 was constructed in this study to get a fixed-biofilm reactor with merit denitrification performance. By adjusting the operation parameters, it can be concluded that when the carbon to nitrogen (C/N) ratio was 1.5, the hydraulic retention time (HRT) was 6.0 h, and the pH was 6.0, the nitrate removal efficiency (NRE) of the fixed-biofilm reactor was up to 95.4% (2.95 mg L

To replace cutterhead worn tools conveniently or get rid of shield’s jamming effectively in complicated stratum, a new nonlinear cutterhead pose control system of large-diameter slurry shields is especially designed. High precision cutterhead pose control of large-diameter slurry shields is hardly achieved due to the uncertain load force and mass. A nonlinear controller constructed by adaptive robust control based on sliding mode is designed for this parallel mechanism, which includes a special adaptation law to compensate for the uncertainties. The stability of the whole closed loop system is verified based on Lyapunov theory. And the validity of the proposed strategy is proved by Simulink and AMESim co-simulation. The simulation results show that not only in control accuracy but also in parameter uncertainty, the designed nonlinear cutterhead pose control is effective.

To conveniently replace worn cutterhead tools in complicated strata, a novel cutterhead attitude control mechanism was recently designed. Meanwhile, the mechanism also causes an engineering problem of how to control a matching cutterhead anti-torque system (CATS) effectively, which is used to prevent a drive box of the cutterhead from rotation during a complex excavation process. In this paper, a disturbance observer-based adaptive position controller is proposed for the CATS. The proposed method presents a nonlinear adaptive controller with adaptation laws to compensate for the unknown time-varying load torque and damping uncertainty in the system. Based on the disturbance observer method and sliding mode control, an asymptotically stable controller proven by Lyapunov theory is constructed using the back-stepping technique. In addition, a virtual test rig based on MATLAB and AMESim co-simulation is built to verify the validity of the proposed controller. The simulation results show that the proposed method has good performance for tracking tasks in the presence of uncertainties compared with PID control. Together, the data support targeting disturbance observer-based adaptive position control as a potential control strategy for cutterhead anti-torque systems.

In this study, a nitrate-dependent ferrous (Fe

An iodine-mediated oxidative cyclization reaction between 2-(pyridin-2-yl)acetate derivatives and different alkynes has been developed, which provides regioselective and chemoselective syntheses of multiply substituted indolizines under modified reaction conditions. Plausible mechanisms have been proposed to explain the selective syntheses of indolizines. This protocol can be also applied to the stepwise synthesis of 2,2′-biindolizines.

An I2/CuI-promoted multi-component reaction from pyridines, aryl methyl ketones and electron deficient acrylates has been accomplished in a “one-pot” manner, which provides a straightforward and efficient access to C-3 acylated indolizines. The key intermediate of N-ylides is hypothesized to be generated in situ from pyridines and (hetero)aryl methyl ketones in the presence of iodine. This method has been applied in the synthesis of two molecules with anticonvulsant and anti-inflammatory activities.

A kind of gel beads loaded with iron–carbon powder (Fe–C), Zoogloea sp. L2, and riboflavin (VB2) were prepared through cross–linking of sodium alginate (SA) to establish an immobilized bioreactor. The optimal ratio of SA beads was adjusted by orthogonal experiment. The change of oxidation–reduction potential (ORP) and the concentration of Fe2+ and Fe3+ showed that the addition of VB2 as a redox mediator can promote denitrification. Under the optimal conditions (carbon to nitrogen (C/N) ratio = 2.0, pH = 7.0, and hydraulic retention time (HRT) = 8 h), the nitrate removal efficiency (NRE) of bioreactor reached 98.48% (1.99 mg L–1h−1). Furthermore, Fourier transform infrared spectrometer (FTIR), Fluorescence excitation–emission matrix (EEM), X–ray diffraction (XRD), and gas chromatography (GC) analysis revealed that the immobilization and denitrification of the immobilized bioreactor were excellent. High throughput sequencing also showed that Zoogloea played a vital role in nitrate removal.

Data mining is extracted from a large number of incomplete, noise, broadcast and random data hidden in it. There are many terms similar to knowledge discovery in database, data analysis, data merging and decision support. Like mining, people use raw data as a source of knowledge. The original data can be used as relational or semi-structured database data structure in the form of text, image, image or impurity data published on the Internet. The method of discovering knowledge can be mathematical or non mathematical, inferential or inductive. The discovered knowledge can be used in information management, request optimization, decision support, process control, and data maintenance and management. In this paper, decision tree algorithm and acupuncture prescription model are used to carry out a series of research. Data mining is a wide range of technical category summary, which has intelligent, mathematical statistics, database, parallel computing and decision tree algorithm in the field of engineering and technical personnel. The new information processing technology data mining technology is good at extracting, integrating and inferring the knowledge in text data from large data. This technology has obvious advantages for needle data processing. The analysis of complex meridians, meridian blood, diseases, medical records and other data related to acupuncture is suitable to show the scientific significance of acupuncture theory. This paper is based on the compatibility of data mining technology in acupuncture and moxibustion.

The pollution of multifarious pollutants such as heavy metal, organic compounds, and nitrate are a hot research topic at present. In this study, the functions of Zoogloea sp. MFQ7 and its biological precipitation formed during bacterial manganese oxidation on the removal of phenol and 17β-estradiol (E2) were investigated. Strain MFQ7, a manganese-oxidizing bacteria, can remove 98.34% of phenol under pH of 7.1, a temperature of 30 ℃ and Mn

In this study, a nitrate–dependent ferrous (Fe2+) oxidizing strain under anaerobic conditions was selected and identified as XL4, which belongs to Aquabacterium. The Box–Behnken design (BBD) was used to optimize the growth conditions of strain XL4, and the nitrate removal efficiency of strain XL4 (with 10% inoculation dosage, v/v) could reach 91.41% under the conditions of 30.34 ℃, pH of 6.91, and Fe2+ concentration of 19.69 mg L–1. The results of Fluorescence excitation–emission matrix spectra (EEM) revealed that the intensity of soluble microbial products (SMP), aromatic proteins and the fulvic–like materials were obvious difference under different Fe2+ concentration, pH, and temperature. X–ray diffraction (XRD) data confirmed that the main components of bio–precipitation were Fe3O4 and FeO(OH), which were believed to be responsible for the adsorption of phenol and estradiol. Furthermore, the maximum adsorption capacity of bio–precipitation for phenol and estradiol under the optimal conditions were 192.6 and 65.4 mg g–1, respectively. On the other hand, the adsorption process of phenol and estradiol by bio–precipitation confirmed to the pseudo–second–order and Langmuir model, which shows that the adsorption process is chemical adsorption and occurs on the uniform surface.

We investigated the Bayesian model averaging (BMA) technique as an alternative method to the traditional model selection approaches for multilevel models (MLMs). BMA synthesizes the information derived from all possible models and comes up with a weighted estimate. A simulation study compared BMA with additional modeling techniques, including the single "best" model approach, Bayesian MLM using informative, diffuse, and inaccurate priors, and restricted maximum likelihood. A two-level random intercept and random slope model was examined with these modeling techniques. Generated data used two types of true models: a full MLM and a reduced MLM. Findings of the simulation study suggested that BMA was a trustworthy alternative to traditional model comparison and selection approaches through the Bayesian and the frequentist frameworks. We also include an empirical example highlighting the extension of MLMs into the BMA framework, as well as model interpretation.

Although considerable efforts have been made for the development of lanthanide complex-based luminescent probes, a major drawback of the current probes is the requirement for UV excitation. In this work, a visible-light-excited Eu

A palladium-catalyzed ligand controlled regioselective ­coupling reaction of secondary propargyl carbonates and ethyl 2-(pyridin-2-yl)acetate derivatives has been described, leading to C-3 benzyl­ated indolizines for the first time in moderate to good yields. DBFphos as the ligand is crucial to this high regioselective annulation reaction, and a plausible reaction mechanism has been proposed.

Herein, we designed and synthesized a new β-diketonate−Eu3+ complex-based luminescent probe for peroxynitrite (ONOO−), Eu(hdph)3(tpy), by using a 2,4-dimethoxyphenyl-substituted β-diketone ligand 1,1,1,2,2,3,3-hetafluoro-6-(2,4-dimethoxyphenyl)-4,6-hexanedione (hdph) and a coligand 2,2′,2″-terpyridine (tpy). The probe exhibits strong fluorescence with a great quantum yield of 25.6%. Upon the addition of ONOO−, the luminescence of Eu(hdph)3(tpy) at 607 nm was dramatically quenched due to the interaction of the 2,4-dimethoxyphenyl moiety with ONOO−, which leads to the deactivation of the excited Eu3+ complex and a 71-fold luminescence decrease. The dose-dependent luminescence decrease showed good linear relationship against the ONOO− concentration with the detection limit at nano-molar concentration level. In addition, the luminescence response of Eu(hdph)3(tpy) to ONOO− displayed high specificity over various reactive oxygen/nitrogen species. Taking advantage of the high sensitivity and specificity, Eu(hdph)3(tpy) was applied for the time-gated luminescence imaging of ONOO− in HepG2 cells. The results demonstrated the practical applicability of Eu(hdph)3(tpy) as a luminescent probe for the long-term visualization of intracellular ONOO−.

Although considerable efforts have been made for the development of lanthanide complex-based luminescent probes, a major drawback of the current probes is the requirement for UV excitation. In this work, a visible-light-excited Eu3+ complex-based luminescent probe, [Eu(HDPH)3(DPBT)] (HDPH: 1,1,1,2,2,3,3-heptafluoro-6-(2,4-dimethoxyphenyl)-4,6-hexanedione; DPBT: 2-(N,N-diethylanilin-4-yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine), has been designed and synthesized for the highly sensitive and selective time-gated luminescence imaging detection of peroxynitrite (ONOO−) in living cells. The probe exhibits a strong visible excitation peak at 400 nm, with the excitation window extending to beyond 460 nm. Upon reaction with ONOO−, the luminescence of the probe at 610 nm is greatly quenched because the excited state of the Eu3+ complex is deactivated by the interaction between the 2,4-dimethoxyphenyl moiety and ONOO−. The dose-dependent luminescence decrease of the probe shows good linearity with a detection limit of 1.8 μM for ONOO−, and the probe can specifically distinguish ONOO− from other reactive oxygen/nitrogen species (ROS/RNS). The [Eu(HDPH)3(DPBT)]-loaded HepG2 cells were prepared, and then the exogenous ONOO− in HepG2 cells was successfully imaged in time-gated luminescence mode. The photostability results of the [Eu(HDPH)3(DPBT)]-loaded HepG2 cells demonstrate the practical applicability of the visible-light-excited probes for long-term cell imaging.

Acupuncture and moxibustion therapy, as a traditional medical treatment method of the motherland, is widely used in the treatment of mild cognitive dysfunction, with remarkable curative effect, and is increasingly recognized by the medical community. However, so far, there is no acupuncture prescription and acupoint usage rules for acupuncture treatment of mild cognitive impairment. Therefore, it is of great significance to collect, organize and data mining related data in order to summarize the relationship between acupuncture points and mild cognitive dysfunction, and to provide references for clinical treatment. This article standardizes the acupuncture points in the database. This paper uses Excel and SPS software to carry out frequency analysis, cluster analysis and association rules, and draws the rules of acupoints, meridians, positions, frequency of specific acupoints, clustering of acupoints and compatibility. In this paper, the number of cases in the treatment group and the control group, the main acupoints and matching points of the acupuncture prescription, the treatment methods, the efficacy evaluation indicators, and the total effective rate of the treatment group and the control group are extracted into the Excel table to form a mild cognition of acupuncture treatment Prescription database for dysfunction. This article studies the rules and characteristics of acupuncture points derived from data mining, takes the general rules and characteristics of clinical acupuncture and moxibustion treatment as a reference for clinical acupuncture and moxibustion, and verifies it with the results obtained. The experimental results show that in the analysis of association rules, taking Baihui and Shenting as examples, the support degree indicates that the probability that the two acupoints appear in the 126 heads at the same time is 51.83%, and the confidence and support for the occurrence of Baihui and Shenting are relatively high. High, it is considered to be a common compatible point pair for acupuncture treatment of mild cognitive dysfunction.

The Bayesian estimation framework has specific benefits that can aid in the estimation of mixture models. Previous research has shown that the use of priors to capture (un)certainty in latent class...

A metal-free approach to polysubstituted oxazoles via the oxidative coupling of readily available benzylamines and 1,3-dicarbonyl derivatives in the presence of an external base has been developed. A variety of functional groups on both of the starting materials are tolerated using this method, affording the corresponding oxazoles in moderate to good yields. Iodination was proposed as the initiation step of the reaction and a plausible mechanism has been proposed to explain the reaction pathway.

Bimetallic copper-/palladium-catalyzed multicomponent reaction of propargyl carbonates, aryl iodides, and diboron species was studied. This procedure can be used for synthesis of di-, tri-, and tetra-substituted allenes. Using diboronic acid, the reaction is supposed to proceed via allenylboronic acid intermediate.

A Pd-catalyzed regioselective annulation reaction of propargyl carbonates and 2-(pyridine-2-yl) acetonitrile derivatives has been accomplished, which provides a straightforward and efficient access to polysubstituted indolizines. The choice of the phosphine ligand is crucial to the high regio-selectivity of the reaction.