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The aim of this study was to evaluate the efficacy of atorvastatin plus disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). METHODS We queried the PubMed, Embase, Web of Science, and the CENTRAL (Cochrane Central Register of Controlled Trials) databases for this study. The pooled efficacy was evaluated using standardized mean differences. The inverse of the variance model was used for data pooling. RESULTS Based on the search, we identified 9 randomized controlled trials. The trials included 258 patients in the atorvastatin plus DMARD groups and 246 patients in the DMARD alone groups. The primary outcome was the change from baseline in the 2018 (209:228 Disease Activity Score in 28 Joints). Based on the Disease Activity Score in 28 Joints, disease activity in RA patients decreased significantly in patients given atorvastatin plus DMARD compared with patients given DMARD alone (standardized mean difference, -2.46; 95% confidence interval, -3.98 to -0.95; p = 0.0015; I2 = 97%; p < 0.01). Subgroup analysis did not identify any confounding factors, and no publication bias was detected in the meta-analysis. CONCLUSIONS The result supports that atorvastatin could be added to DMARDs to treat patients with RA.

The switch in the substation is operated by remote control. To prevent the on-site personnel from being injured by the explosion of the fault switch, a prompt signal shall be sent to the on-site personnel to remind them to stay away from the operating equipment before the remote operation of the primary equipment is required from the perspective of safety. At present, the method of telephone notification or no notification is adopted, which is low in efficiency and poor in operability, and it is difficult to timely and effectively notify on-site personnel. The on-site prompt device for remote switch operation can send prompt signals to on-site personnel before remote switch operation without increasing any workload by monitoring the message of the station control layer switch, which can prevent personal injury and death caused by the explosion of remote switch operation and is of great significance to safety production.

Highly reactive dicoordinate (i.e., mono-base-stabilized) borylenes of the form [LBR] (L = Lewis base) have recently shown intriguing reactivity with inert small molecules, including N2. However, t...

Zhimin Geng,* Yijing Tao,* Fenglei Zheng, Linlin Wu, Ying Wang, Yujia Wang, Yameng Sun, Songling Fu, Wei Wang, Chunhong Xie, Yiying Zhang, Fangqi Gong Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangqi GongDepartment of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of ChinaTel/Fax +86 571 86670008Email gongfangqi@zju.edu.cnBackground: Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of the body’s innate immune system; however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. We aim to comprehensively delineate monocyte heterogeneity in healthy and KD infants and to reveal the underlying mechanism for KD.Methods: Peripheral monocytes were enriched from peripheral blood samples of two healthy infants and two KD infants. scRNA-seq was performed to acquire the transcriptomic atlas of monocytes. Bio-information analysis was utilized to identify monocyte subsets and explore their functions and differentiation states. SELL+CD14+CD16- monocytes were validated using flow cytometry.Results: Three monocyte subsets were identified in healthy infants, including CD14+CD16- monocytes, CD14+CD16+ monocytes, and CD14LowCD16+ monocytes. Cell trajectory analysis revealed that the three monocyte subsets represent a linear differentiation, and possess different biological functions. Furthermore, SELL+CD14+CD16- monocytes, which were poorly differentiated and relating to neutrophil activation, were found to be expanded in KD.Conclusion: Our findings provide a valuable resource for deciphering the monocyte heterogeneity in healthy infants and uncover the altered monocyte subsets in KD patients, suggesting potential biomarkers for KD diagnosis and treatment.Keywords: Kawasaki disease, monocyte subsets, scRNA-seq

Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to “leak” into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between Enterorhabdus, Parabacteroides and Kyn levels in the brain. Reciprocal crosstalk between the brain and gut was further validated by citalopram treatment, IDO inhibitor and microbiota intervention, which counteracted depression-like behavior, Kyn metabolic signaling and microbiota composition in CRS mice. Meanwhile, Parabacteroides treatment affected Trp metabolism in mouse hippocampus, manifesting as elevated concentration of 5-HT as well as ratio of 5-HT to Trp. These results suggest that long-term stress disrupts Kyn metabolism and endocrine function along the gut-brain axis, accompanied by the disrupted homeostasis of certain microbiota, which collectively contribute to the development of depression-like behavior.

Transition metal-free direct and base-catalyzed 1,2-diborations of arylacetylenes using pinB-BMes2 provided a syn/anti-isomeric mixture of diborylalkenes. The kinetic analysis showed that the reaction rate and isomer ratio were affected by reaction conditions and substituents on the aryl ring. DFT calculations indicated that direct addition proceeded via the interaction of acetylene-π with the BMes2 fragment. In contrast, for the base-catalyzed diboration, the previously isolated sp2–sp3 diborane and borataallene were confirmed as stable intermediates by calculations. The whole reaction pathways can be divided into the Bpin-migration and deprotonation steps, where the borataallene should be considered as a common intermediate. It should be noted that the deprotonation step is reversible and affords the kinetically less favoured isomer under the thermodynamic conditions. As a result, the composition of isomeric products, in the base-catalyzed diboration, is attributed to the small difference of activation barriers between direct and base-catalyzed systems.

To improve the performance and application value of recycled plastics, filling modification has been widely used in waste plastic reinforcement. In this study, recycled polyethylene (RPE) was reinforced via extrusion blending using waste polyester fiber (WPF) from a waste silk wadding quilt as a reinforcer. The effects of the amount of WPF on the mechanical properties, the thermal stability of RPE and the microstructure of the RPE/WPF composite were studied. The result shows that extrusion blending can evenly disperse WPF in RPE matrix and that WPF can clearly improve the tensile strength, flexural modulus, storage modulus and thermal stability of RPE. The tensile strength and flexural modulus almost achieved the maximum when the addition of WPF was 20 wt%. The storage modulus under this condition is also higher than that of other samples. This study provides a cheap and effective reinforcement method for waste plastics as well as a new idea for the reuse of WPF, which is of great significance to the reuse of waste and environmental protection. However, how to enhance the interface adhesion between WPF and RPE to further improve the enhancement effect needs further research.

Proteins with a changeable conformation, such as polymerases, play a very important role in various life activities. Their conformational changes can be reflected in their structural size and flexibility, which may influence their transport kinetics. Recently, solid-state nanopore sensors have been widely applied to characterize the conformation of proteins and other complex structures as sensitive and high throughput single-molecule detectors. In this work, we used a SiN nanopore sensor to study the conformational changes between the Klenow fragment (KF) and its monomer complex with a DNA substrate (KF-DNA). By calculating their hydrodynamic radii, pore volume, the duration of translocation events, drift velocity, and molecular dynamics simulations, we found that the KF-DNA monomer complex has a tighter structure and transports slower. The study performed here can be potentially used to identify single polymerases in real time and may ultimately reveal conformation changes and the interaction between polymerases and their substrates.

Antimony mining activities can result in serious contamination of soil by heavy metals, which represents a risk to human health. In this study, the contamination and sources of 14 heavy metals, and their risks to both ecosystem and public health from these metals at an antimony mining site in Guizhou Province in China were explored. The results showed that the mean concentrations of Hg, Cu, As, Se, Cd, Sn, Sb and Pb were 3.73, 2.49, 13.99, 38.32, 1.11, 1.61, 305.33, 1.59 times than their local background levels. Sb, Se, As and Hg presented the relatively heavy pollution, wherein Sb (EI = 2137.34 320), Hg (EI = 150.26 80) and As (EI = 139.92 80) also posed the strong ecological risk. The sources identification illustrated Hg, Pb, As, Bi, Cr, Sb, Cd and Zn were attributed to industrial activities, Ni, Co, Au and Cu (p 0.01) were derived from a combination of a lithogeny origin and anthropogenic source, whereas Se was of natural origin. Health risk assessment demonstrated that Ni, Cr and As presented both the unacceptable noncarcinogenic and carcinogenic risk, and Sb (HI = 1.44E+03) and Cd (HI = 2.91E+00) posed unacceptable noncarcinogenic risk to the local resident. Furthermore, children in the 1-6 age group (HI = 7.83E+02) were more sensitive to noncarcinogenic risk, and the 6-18 age group (CRI = 2.39E-02) as more prone to carcinogenic risk. The dermal contact was the predominant exposure pathway of noncarcinogenic and carcinogenic risks with a contribution rate of over 97% for all age groups. Overall, this research provided the comprehensive information on heavy metals in an antimony mining sites, and the related heavy metals should be paid attention for ensuring soil safety and protecting local people's health.

A systematic theoretical study has been performed with the aid of density functional theory (DFT) calculations on the mechanism of asymmetric 1,4-dearomatization of free pyridine with styrene and d...

In order to solve the problem that low classification accuracy caused by the different distribution of training set and test set, an unsupervised domain adaptation method based on discriminant sample selection (DSS) is proposed. DSS projects the samples of different domains onto a same subspace to reduce the distribution discrepancy between the source domain and the target domain, and weights the source domain instances to make the samples more discriminant. Different from the previous method based on the probability density estimation of samples, DSS tries to obtain the sample weights by solving a quadratic programming problem, which avoids the distribution estimation of samples and can be applied to any fields without suffering from the dimensional trouble caused by high-dimensional density estimation. Finally, DSS congregates the same classes by minimizing the intra-class distance. Experimental results show that the proposed method improves the classification accuracy and robustness.

To determine the operating region of modular multilevel converter (MMC) station under unbalance grid conditions, this paper proposes the analytical and point-scanning methods. First, the imbalance of PCC voltages is expressed in terms of two proposed indexes for single phase fault (SPF), which can be directly calculated from the grid parameter and grounding impedance. Next, the algebraic equation to solve the PCC voltage for the given PCC power is presented. The existence of PCC voltage is considered as one constraint. Moreover, the other constraints for transformer rating, converter rating, ac current and output voltage are also analyzed to adapt the unbalance conditions. Based on the proposed method, the effect of the grid imbalance on the operating region of MMC is analyzed and then the common constraints to confine the operating region are determined. Following that, the boundary control is proposed to limit the operation of MMC on the boundary of the operating region under unbalanced conditions. The open and modular control structure allows more constraints to be considered for the boundary control. The simulation results validate the correctness of the proposed methods to define the operating region and the effectiveness of the boundary control.

BMP4 regulates a plethora of developmental processes, including the dorsal-ventral axis and neural patterning. Here, we report that BMP4 reconfigures the nuclear architecture during the primed-to-naive transition (PNT). We first established a BMP4-driven PNT and show that BMP4 orchestrates the chromatin accessibility dynamics during PNT. Among the loci opened early by BMP4, we identified Zbtb7a and Zbtb7b (Zbtb7a/b) as targets that drive PNT. ZBTB7A/B in turn facilitate the opening of naive pluripotent chromatin loci and the activation of nearby genes. Mechanistically, ZBTB7A not only binds to chromatin loci near to the genes that are activated, but also strategically occupies those that are silenced, consistent with a role of BMP4 in both activating and suppressing gene expression during PNT at the chromatin level. Our results reveal a previously unknown function of BMP4 in regulating nuclear architecture and link its targets ZBTB7A/B to chromatin remodelling and pluripotent fate control.

Metal-oxide catalysts have great potential in efficient CO2 electroreduction (CO2ER). Unfortunately, many catalysts exhibit limited selectivity for carbon products at the high current density. Here, density functional theory is applied to analyzethe active sites on SnO2 matrix surface. The theoretical analysis indicates that the elimination of oxygen atoms from SnO2 matrix can significantly improve CO2 activation and suppress H2. Inspired by the analysis, a series of defect-engineered SnO2 nanocubes are synthesized. The as-prepared SnO2 with rich oxygen vacancy (Vo-rich SnO2) possesses C1 selectivity of 92.5% at −44.2 mA cm−2 which is higher than pristine SnO2 (78.1% at −18.2 mA cm−2), and reaches 30 h stability. Furthermore, the CO2ER activity in a 10% CO2 atmosphere is studied for the first time, where Vo-rich SnO2 demonstrates C1 selectivity of 74.5%. This work testifies the potential of theory-guided strategy to design practicaltin-oxide electrocatalysts and firstly highlights the research of industrial flue gas for CO2ER.

High-performance electrode materials derived from biomass for supercapacitors have been considered as an effective solution to the problems of the fossil energy shortage and the environment deterioration. Most importantly, the specific capacitance, rate performance and cyclic stability for these electrode materials are focused issues. Here, we prepare a new type porous carbon using laminaria japonica as the carbon source via a simple carbonization and activation method, and investigate its morphology, structure and electrochemical properties. The results show that the porous carbon materials exhibit amorphous structure, high specific surface area with abundant pores and oxygen functional groups. The specific capacitance of the porous carbon with a large specific surface area of 1902.42 m2 g−1 and total pore volume of 1.26 cm3 g−1 can reach to 192 F g−1 at 0.1 A g−1. Furthermore, this porous carbon possesses a specific capacitance of 120 F g−1 at 10 A g−1, nearly 100% capacitance retention rate and coulomb efficiency after 10000 cycles at 1 A g−1, indicating excellent rate performance and cyclic stability. Therefore, as-prepared porous carbons derived from laminaria japonica with low cost, easy availability, high regeneration ability and sustainability have a promising application as the electrode materials for supercapacitors.

In this paper, we shall extend some results regarding the growth estimate of entire solutions of certain type of linear differential equations to that of nonlinear differential equations. Moreover, our results will include several known results for linear differential equations obtained earlier as special cases.

A series of fractional robust trajectory tracking controls are proposed for the Delta parallel robot with uncertainty. For the high speed and heavy load, the Delta parallel robot could not ignore the influences of the high nonlinearity (by the dynamics of the multiple closed-loops mechanism and the nonlinear joints friction) and the various kinds of uncertainties (i.e., the unknown dynamic parameters and external disturbances caused by the residual vibration). By formulating the motion equation of the Delta parallel robot, the nonlinearity is settled by a norm model based control design. The uncertainty considered in the paper is time-varying but unknown. An online estimation with an exponential type leakage term and dead-zone is construct to investigate the realtime information of the uncertainty. In virtue of the estimated information, two fractional robust trajectory tracking controls with the joints friction compensation are designed. Under the proposed controls, the system performance of the Delta parallel robot can be deterministically guaranteed (which includes uniform boundedness and uniform ultimate boundedness).

Objective: To assess the impact of applying published fetal growth references or standards in the Chinese mainland population and to compare their ability to predict newborns small- for- gestational- age (SGA). Design: Retrospective observational study. Setting: A tertiary hospital in Shenzhen, a Chinese city with the most immigrants. Population: All pregnant women (n=106,455) who booked for prenatal care with ultrasound measurements for fetal biometry between 2012 and 2019. Methods: A fractional polynomial regression model was applied to construct Shenzhen fetal growth chart ranges for HC, BPD, AC, and FL. The differences between Shenzhen charts and published charts were quantified by calculating the Z-score. Main outcome measures: The impact of applying these published charts was quantified by calculating the proportions of fetuses with biometric measurements below the 3rd centile of these charts. The sensitivity and area under the receiver operating curves of published charts to predict neonatal SGA (birthweight

Industry wastewater is considered one of the worst polluters of our precious water ecologies. However, the types of pollutants present in wastewater from industrial wastewater treatment plants (IWTPs) are still unclear. In this study, a simple and effective chemical fingerprinting method for checking the source-sink relationships among different industrial wastewaters and their effluent-receiving river was established. 107, 228, 155, and 337 chemicals were screened out in wastewater from electronics, steel, textile, and printing and dyeing plants, respectively. Chemical fingerprinting of the detected chemicals was performed, and results showed that aromatic compounds were the most prevalent among the pollutant categories (i.e., 56, 189, and 168 in electronics, iron and steel, and printing and dyeing plants, respectively). The traceability analysis of the chemicals selected in the effluent determined the characteristic pollutants of different industrial enterprises. Sixty-eight compounds were identified as the characteristic pollutants in the different process stages of wastewater of the four IWTPs. Of the 84 effluent-receiving river water signature pollutants, 47.6% (n = 40) were also detected in the effluent from the four IWTPs. Effective screening of organic pollutants in industrial wastewater and determining their sources will help accelerate the improvement of industrial wastewater treatment technology.

The accuracy of doubly fed induction generator (DFIG) models and parameters plays an important role in power system operation. This paper proposes a parameter identification method based on the hybrid genetic algorithm for the control system of DFIG converters. In the improved genetic algorithm, the generation gap value and immune strategy are adopted, and a strategy of “individual identification, elite retention, and overall identification” is proposed. The DFIG operation data information used for parameter identification considers the loss of rotor current, stator current, grid-side voltage, stator voltage, and rotor voltage. The operating data of a wind farm in Zhangjiakou, North China, were used as a test case to verify the effectiveness of the proposed parameter identification method for the Maximum Power Point Tracking (MPPT), constant speed, and constant power operation conditions of the wind turbine.

The paper proposes a formation tracking control method for the uncertain artificial swarm systems under the inequality constraints. Not only can the agents perform swarm behaviors (e.g., convergence, formation and avoidance of collision), but they can also track the fixed targets in a constrained area (which is formulated as the inequality constraints, such as unilateral constraint and bilateral constraint.). The swarm behaviors are creatively considered as the servo constraints or the control objectives for the swarm agents. Based on the Udwadia-Kalaba (U-K) equation, those prescribed behaviors are realized by a model-based control design (that is the servo constraints force model-based feedforward control). To deal with the inequality constraints in the formation tracking process, a differential homeomorphism transformation is used to relieve the environmental constraints for the swarm agents. Moreover, the uncertainty of the swarm agents (i.e., the parameter uncertainty in modeling and the external disturbances) is considered, which is time-varying and unknown (but bounded). An uncertainty estimation method with dead-zone and leakage term is designed to calculate the possible upper bound of the uncertainty. In virtue of the estimated upper bound of the uncertainty, a robust control is designed for the uncertain swarm agents to obey the prescribed swarm behaviors in the formation tracking task. The system performances of the artificial swarm systems under the proposed control are theoretically guaranteed by a range of rigorous theorems and numerically verified by the simulations of three agents.

In this study, ultrasonic pulse velocity (UPV) and ultrasonic shear-wave tomography are combined to measure the residual compressive strength (RCS) of small-scale lining concrete blocks and to detect inner defects in the lining structure. The characteristics of and variations in the RCS of test blocks after being exposed to elevated temperatures (200–800 °C) and constant heating times (2 h, 3 h, and 4 h) were studied. At 800 °C, the RCS values reduced by 64.4%, 69.2%, and 74.6% at heating times of 2 h, 3 h, and 4 h. Scanning electron microscopy (SEM) was used for the micro-phase analysis of the samples that had been exposed to high temperatures. The heating time and RCS as well as the SEM micro-structure relationship were compared. Finally, a tunnel lining slab sample was designed to simulate the post-fire damage inside the blocks. Additionally, shear-wave tomography with 32 probes was able to detect the ϕ10 mm void defects at a depth of 200 mm.

Water elements pollution has attracted public attention globally. Wuxi is located in East China, and its water source, Taihu Lake, has been severely polluted since 2007. Studies of elemental pollution profiles have yet to be conducted in this area. In this study, 56 water samples were collected in 2018, and 33 elements were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that the levels of 33 elements ranged from 1.35 × 10

Due to their wide coverage, low acquisition cost and large data quantity, the mobile phone signaling data are suitable for fine-grained and large-scale estimation of traffic conditions. However, the relatively high level of data noise makes it difficult for the estimation to achieve sufficient accuracy. According to the characteristics of mobile phone data noise, this paper proposed an improved density peak clustering algorithm (DPCA) to filter data noise. In addition, on the basis of the long short-term memory model (LSTM), a traffic state estimation model based on mobile phone feature data was established with the use of denoising data to realize the estimation of the expressway traffic state with high precision, fine granules, and wide coverage. The Shanghai–Nanjing Expressway was used as a case study area for method and model verification, the results of which showed that the denoising method proposed in this paper can effectively filter data noise, reduce the impact of extreme noise data, significantly improve the estimation accuracy of the traffic state, and reflect the actual traffic situation in a fairly satisfactory manner.

To predict grape maturity in solar greenhouses, a plant phenotype-monitoring platform (Phenofix, France) was used to obtain RGB images of grapes from expansion to maturity. Horizontal and longitudinal diameters, compactness, soluble solid content (SSC), titratable acid content, and the SSC/acid of grapes were measured and evaluated. The color values ( R , G , B , H , S , and I ) of the grape skin were determined and subjected to a back-propagation neural network algorithm (BPNN) to predict grape maturity. The results showed that the physical and chemical properties (PCP) of the three varieties of grapes changed significantly during the berry expansion stage and the color-changing maturity stage. According to the normalized rate of change of the PCP indicators, the ripening process of the three varieties of grapes could be divided into two stages: an immature stage (maturity coefficient Mc < 0.7 ) and a mature stage (after which color changes occurred) ( 0.7 ≤ Mc < 1 ). When predicting grape maturity based on the R , G , B , H , I , and S color values, the R , G , and I as well as G , H , and I performed well for Drunk Incense, Muscat Hamburg, and Xiang Yue grape maturity prediction. The GPI ranked in the top three (up to 0.87) when the above indicators were used in combination with BPNN to predict the grape Mc by single-factor and combined-factor analysis. The results showed that the prediction accuracy (RG and HI) of the two-factor combination was better for Drunk Incense, Muscat Hamburg, and Xiang Yue grapes (with recognition accuracies of 79.3%, 78.2%, and 79.4%, respectively), and all of the predictive values were higher than those of the single-factor predictions. Using a confusion matrix to compare the accuracy of the Mc’s predictive ability under the two-factor combination method, the prediction accuracies were in the following order: Xiang Yue (88%) > Muscat Hamburg (81.3%) > Drunk Incense (76%). The results of this study provide an effective way to predict the ripeness of grapes in the greenhouse.

The phenomenon of three phase voltage imbalance frequently occurs in large-scale new energy grid connected areas in China; in severe cases, a large number of wind turbines will be disconnected from the grid. To solve the problem of the voltage imbalance at the point of common coupling (PCC), analyze the influence of generator parameters change on negative sequence voltage under the background of unbalanced power grid, a modeling method of base-frequency negative sequence impedance of doubly fed induction generator (DFIG) which including phase locked loop (PLL), rotor side converter (RSC) and grid side converter (GSC) is proposed. By establishing the negative sequence equivalent circuit of grid-connected system of DFIG, the relationship between the negative sequence voltage of PCC and the negative sequence impedance of DFIG is listed, and analyzing the sensitivity of control parameters link to base-frequency impedance, the parameter that has great influence on base-frequency negative sequence impedance of PCC is found out. Finally, the accuracy of impedance modeling and sensitivity analysis is verified by simulation studies.

Shengmai San, a well-known traditional Chinese medicine formula, is used to treat coronary heart diseases and myocardial infarction. The complex composition and complicated mechanism of the Shengmai preparations bring a significant challenge in the development of a suitable quality control method.This work aims to establish a chromatographic fingerprinting method and propose a weighting algorithm for application in fingerprint similarity analysis to ensure consistent quality of the Shengmai capsule.A chromatographic fingerprint method was established using tandem UV/charged aerosol detection (CAD) for Shengmai capsule quality control. After method verification, the developed method was applied to analyze 15 batches of the samples. Then a weighting algorithm of the fingerprint peak was proposed and used for the fingerprint similarity analysis.An HPLC-UV/CAD fingerprint method was successfully developed for the Shengmai capsules. Chromatographic conditions of the HPLC-UV/CAD method were optimized with a definitive screening design, and the optimized ranges of operating parameters were obtained with a Monte Carlo simulation method. The combined use of the proposed weighting algorithm and similarity analysis on fingerprint data improves the sensitivity of distinguishing batch-to-batch quality differences.The developed HPLC-UV/CAD fingerprint method is robust, reliable, and efficient. The proposed weighting algorithm combined with similarity analysis is promising and meaningful for the quality consistency assessment of HPLC-UV/CAD fingerprints.

Gestational diabetes mellitus (GDM) is an important metabolic complication of pregnancy, which affects the future health of both the mother and the newborn. The pathogenesis of GDM is not completely clear, but what is clear is that with the development and growth of the placenta, GDM onset and blood glucose is difficult to control, while gestational diabetes patients’ blood glucose drops and reaches normal after placenta delivery. This may be associated with placental secretion of insulin-like growth factor, adipokines, tumor necrosis factor-α, cytokines and insulin resistance. Therefore, endocrine secretion of placenta plays a key role in the pathogenesis of GDM. The influence of DNA methylation of these molecules and pathway-related genes on gene expression is also closely related to the pathogenesis of GDM. Here, this review attempts to clarify the pathogenesis of GDM and the related maternal and placental DNA methylation changes and how they affect metabolic pathways.

Preeclampsia (PE), a systemic vascular disorder, is the leading cause of maternal and perinatal morbidity and mortality, and its pathogenesis has yet to be fully elucidated. Siglec6, a transmembrane protein, is highly expressed in human placental trophoblasts, and previous studies have shown that Siglec6 overexpression correlates with PE, but the role of Siglec6 during PE progression is unknown. Here, we demonstrated that the mRNA and protein expression levels of Siglec6 were upregulated in early-onset PE placentas compared with uncomplicated pregnancies, and Siglec6 was primarily located in syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). Moreover, our results showed that chemical reagent-induced HIF-1α accumulation promoted the mRNA and protein levels of Siglec6 in HTR8/SVneo and BeWo cells. Although Siglec6 overexpression did not affect HTR8/SVneo cell proliferation, migration, and invasion, the conditional medium derived from the Siglec6 overexpressed HTR8/SVneo cells (Siglec6-OE-CM) significantly impaired the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, the transcriptome sequencing results revealed that Siglec6 overexpression led to the downregulation of Wnt6 in HTR8/SVneo cells, which was further confirmed by qPCR and ELISA. Recombinant human Wnt6 reversed Siglec6-OE-CM-mediated suppression of HUVEC functions by reactivating the Wnt/β-catenin signaling pathway. Altogether, our study found that elevated trophoblastic Siglec6 contributed to the impairment of vascular endothelial cell functions by downregulating Wnt6/β-catenin signaling.

Lability and bioaccessibility of anthropogenic toxic heavy metals in arid calcareous soils are critical to understand their ecological and health risks. This study examined toxic heavy metal speciation in the calcareous soil contaminated by nonferrous metal smelting. Results demonstrated that approximately 70 years' nonferrous metal smelting and mining in Baiyin led to significant contamination of nearby soil down to about 200 cm depth by cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn), with more serious contamination in the downwind areas of smelting or mining. More than half of Cd, Cu, Pb, and Zn in the soil was present in the labile fractions while more than 75% of cobalt (Co), chromium (Cr), nickel (Ni), and vanadium (V) was present in the residual fraction. Carbonate minerals in this calcareous soil play an important role in the labile fractions, with approximate 25% of Cd and Pb and 15% of Cu and Zn bound in carbonates. Bioaccessible Cd, Cu, Pb, and Zn in the soil were approximately 49.8%, 29.4%, 12.2%, and 33.8% in gastric phase and 13.5%, 15.9%, 4.3%, and 9.1% in intestinal phase of their total concentrations, respectively. Therefore, Cd and Zn were removed from gastric solution to a greater extent than Cu and Pb by neutral intestine environment. However, bioaccessible Co, Cr, Ni, and V in the soil were less than 3% of their total concentrations. Bioaccessibility of these metals but Cu in this calcareous soil was significantly lower than that for the acidic Ultisols and Alfisols in U.S. The concentrations of Cd, Cu, Pb, Zn, and Ni in each chemical and bioaccessible forms were significantly correlated linearly with their total concentrations in the calcareous soil, while only residual concentration was significantly correlated with the total concentration for Co, Cr, and V. These linear slopes showed that relative lability and bioaccessibility increased for Cd, but decreased for Cu, Pb, and Zn with the increase in their total concentrations in the calcareous soil. Direct oral soil ingestion would not pose a non-carcinogenic health risk to local children. However, very high potential ecological risk would be caused by these metals in the soil. These results provide improved insights into the biogeochemical processes of anthropogenic toxic heavy metals in the arid calcareous soils worldwide.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma and has a poor prognosis. However, its underlying mechanisms remain unclear. The present study aimed to evaluate the role of small proline-rich repeat protein 3 (SPRR3) in the proliferation, migration and invasion of ccRCC cells and to investigate its upstream and downstream regulatory mechanisms. Survival analysis was performed using the UALCAN website based on the The Cancer Genome Atlas database. Normal renal cell line HK-2 and ccRCC cell lines (786-O, CaKi-1 and UMRC-2) were used. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect mRNA and microRNA (miRNA) levels. Western blotting was used to detect protein levels. Cell Counting Kit-8 and colony formation assays, a wound healing assay and a Transwell invasion assay were used to assess the proliferation, migration and invasion of ccRCC cells, respectively. Transfection of overexpression plasmids and small interfering RNAs were used to upregulate and knockdown SPRR3 expression, respectively. Transfection of miRNA-mimics was used to overexpress miR-338-3p. A luciferase reporter gene assay was used to verify the predicted binding relationship between SPRR3 mRNA and miR-338-3p. The results indicated the following: i) SPRR3 was a risk factor for the survival of patients with ccRCC, and was upregulated in ccRCC cell lines; ii) SPRR3 promoted the proliferation, migration and invasion of ccRCC cells; iii) SPRR3 regulated the tumor phenotypes of ccRCC cells via the PI3K/Akt pathway; iv) miR-338-3p directly targeted SPRR3 mRNA and negatively regulated SPRR3 expression; and v) miR-338-3p inhibited the PI3K/Akt pathway and the tumor phenotypes of ccRCC cells by downregulating SPRR3. In conclusion, SPRR3, as a novel target of miR-338-3p, regulated the proliferation, migration and invasion of ccRCC cells via the PI3K/Akt pathway; this finding not only enriches our understanding of the mechanism underlying ccRCC development, but also demonstrates a potential novel therapeutic target for this disease.

A comprehensive workflow for suspect screening and non-target screening with gas chromatography coupled with quadrupole time-of-flight mass spectrometry (GC/QTOF-MS) was used to characterize the pollution characteristics of soil samples in a typical coking plant in China. Suspect screening confirmed 57 chemicals including PAHs, alkyl PAHs, and phthalates contained in high-resolution personal compound database and library (PCDL). Non-target screening detected 88 chemicals from soil samples in the NIST 17 library. A total of 122 chemicals were screened in soil samples, and many of them were of emerging concern. Their presence in the soil obtained from coking operations has been underestimated, such as the oxygenated PAHs (naphtho[2,1-b]furan and 9H-fluoren-9-one), and the alkyl biphenyls compounds (4,4′-dimethylbiphenyl, 3,3′-dimethylbiphenyl, 4-methyl-1,1′-biphenyl and 2,2′,5,5′-tetramethyl-1,1′-biphenyl). Toxicity assays by luminescent bacteria proved that the extracts from soil samples at different depths showed varying toxicity to V. qinghaiensis sp.-Q67. Soil extracts from a depth of 20–40 cm exhibited the greatest toxicity to luminescent bacteria compared with the other six-layered soil samples, which was correlated with the number of detectable pollutants and total organic carbon content. This study provided a screening method for suspect and non-target contaminants in urban industrial soil sites, which was important in identifying localized contamination sources.

Background Retinopathy of prematurity (ROP) continues to be a major cause of visual impairment and blindness in premature infants and children. Objectives To investigate the incidence of severe ROP receiving treatment in extremely preterm (EP) infants in China over time. The risk factors for ROP treatment were also assessed. Methods This was a multicentre retrospective study and a subanalysis of baseline data from the "Outcomes of EP infants in China 2010-2019" study. This study was conducted in 68 tertiary neonatal care centres from 31 provinces of China. Infants with a gestational age of 230 -276 weeks and admitted to a neonatal unit within the first 72 h of life between 2010 and 2019 were enrolled. Incidence of ROP was analysed in infants who survived to 32 weeks postmenstrual age and screened for ROP. Multivariable modified Poisson regression models were used to identify risk factors for ROP treatment. Results Among 7295 eligible infants, 4701 (64.5%) survived to 32 weeks postmenstrual age and met ROP screening criteria. Of the 3756 infants who screened and with ROP data, 2320 (61.8%) developed ROP of any stage. The overall incidence of ROP treatment was 12.6%, decreasing from 45.5% at 23 weeks to 8.3% at 27 weeks. During the 10-year period, the incidence of ROP treatment did not change, although the incidence of any ROP increased over time. Independent risk factors associated with ROP treatment included lower gestational age, small for gestational age, multiple birth, severe intraventricular haemorrhage, patent ductus arteriosus and supplemental oxygen duration. Conclusions The incidence of EP infants receiving ROP treatment showed no change during this 10-year period in China. Prevention of prematurity and foetal growth restriction, judicious use of oxygen and reducing comorbidities are promising factors that may reduce the incidence of ROP needing treatment in these high-risk infants.