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Background We have previously shown that P2X7R/NLRP3-mediated signaling pathway plays an important role in CP chronic inflammation and fibrosis. Inspired by the traditional Chinese medicine(TCM) theory “Chaihu Guizhi Decoctio(CGD)for the treatment of Sudden pain in the heart or abdomen". Targeting in central sensitization(CS) may explain the treatment of Chaihu Guizhi Decoction (CGD) on CP-induced pain. Methods Fifty male SD rats were randomly and equally divided into two groups based on table of random numbers: TNBS group (n = 40) and sham group (n = 10). At 4w after TNBS model, rats in TNBS (n = 40) and sham group (n = 10) were each further divided for drug injection: TNBS-CGD medium dose(n = 10) and TNBS-CGD high dose group(n = 10):The rats were intragastrically treated with CGD(8g,16g.kg− 1,2W, twice a day). TNBS-BBG group(n = 10), the rats were repeated intraperitoneal injection of BBG (P2X7R inhibitor, dissolved in normal saline, 100 ug/10 mL per rat) or sham operated rats (n = 10) were given 0.9% saline solution.After behavioral tests, at 6 weeks, all the rats including TNBS, and sham rats were sacrificed for further experiments. Pancreatic histology was evaluated with hematoxylin and eosin staining, The expression of PGP9.5, α-SMA, NLRP3 and P2X7R proteins and their molecular effects were detected by immunohistochemical staining, immunofluorescence, Western blot. Results Behavioral study indicated that compared to the sham, CGD significantly decreased TNBS-induced mechanical allodynia at 2w after administration and this effect was dose-dependent(response frequencies: 71 ± 20% vs 28 ± 13%). CGD alleviated pancreatic injury in chronic pancreatitis rat, including atrophy, inflammatory cells infltration, fibrosis, the infiltration of inflammatory cells around pancreatic nerves (PGP9.5)and α-SMA expressions (2.5 ± 0.7 vs 1.5 ± 0.6,3.1 ± 0.8 vs 1.6 ± 0.7,3.2 ± 1.0 vs 1.8 ± 1.3, 20.6 ± 4.2 vs 3.0 ± 1.4, 23.8 ± 7.8% vs 4.9 ± 1.6% ). Western blot, IHC and IF data showed that CGD could significantly block expressions P2X7R,NLRP3 protein (P2X7R: 5.1 ± 0.5% vs 3.2 ± 0.1%,NLRP3:28.0 ± 4.3% vs 12.3 ± 1.5%). Conclusions Our findings indicated that CGD could be a novel and effective treatment for CP-induced chronic pain.

Informal settlements in developing megacities are often vulnerable to extreme heat and other environmental hazards. Yet, understanding of this vulnerability remains limited due to inadequate attention to the relationships between characteristics of the built environment and land surface temperature. To address this, we focus on the Mumbai region and employ a Geographically Development-Weighted Regression model that can link land surface temperature with datasets that can capture key characteristics of the built environment, particularly formal or informal settlement types and infrastructure quality. We find the existence of spatial heterogeneity in these relationships suggesting that informal settlements are correlated with higher land surface temperatures, especially under low development conditions. We also find that this effect grows with settlement size, and that the growth in these settlements would increase land surface temperature. We conclude with some guidance for planners and policymakers.

Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear.This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model.Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 μg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin DThe pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VDThese results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD

T-cell lymphoblastic lymphoma (T-LBL) is a class of highly aggressive hematologic neoplasms originating from progenitor T-lymphocytes. MicroRNA (miRNA) is an endogenous RNA molecule with 22 nucleotides in length. Accumulated evidence suggests that miRNA functions as a key regulator in human cancer. Herein, by in silico analysis, we found that miR-211 was a decreased miRNA in T-LBL in high-throughput sequencing data, which was subsequently verified in our cohort. Low miR-211 was closely correlated with bulky disease, high ann arbor stage, relapse and poor prognosis. miR-211 was regulated by N6-methyladenosine (m6A) modification, specifically, m6A methyltransferase METTL14 methylated primary miR-211 (pri-miR-211), expediting pri-miR-211 processing via recruiting DGCR8. Functionally, miR-211 overexpression significantly reduced T-LBL cell viability, DNA synthesis rate and spheroid formation ability, whereas silencing of miR-211 had the opposite effects. In addition, we established the xenograft tumor model and found that miR-211 remarkably inhibited tumor growth in vivo. Further, TCF12 was the direct target of miR-211, miR-211 bound to TCF12 mRNA 3`-untranslated region (UTR) and increased its decay, overexpression of TCF12 could effectively rescue the weakened malignant behavior of T-LBL cells caused by miR-211 overexpression. Collectively, our data clearly demonstrate that miR-211 is a novel tumor suppressor in T-LBL, targeting of miR-211/TCF12 axis may be a potential treatment for T-LBL patients.

Due to its special partitioned stator structure and multi-excitation with two different types of permanent magnet, a new double-stator multi-excitation flux-switching machine (DSME-FSM) has advantages of high torque density, wide speed range, and low cost. For this kind of machine with complex structure, in order to realize the optimization accurately and efficiently, a multi-objective comprehensive optimal design method considering the different weights of the design objectives is presented based on parameters sensitivity analysis and genetic algorithm optimization in this paper. The parametric model of the machine is built up, and a trade-off objective function considering the different weights of the design objectives is defined. The key size parameters with strong sensitive are selected through parameters sensitivity analysis and then optimized by using the genetic algorithm method. The performance comparison between the initial and the optimized machines verifies the proposed optimization method. The anti-demagnetization property and the flux-weakening capability for a wide-speed range operation are also analyzed, which further confirms the DSME-FSM an interesting candidate for EV propulsion.

Given the important role of green environments playing in healthy cities, the inequality in urban greenspace exposure has aroused growing attentions. However, few comparative studies are available to quantify this phenomenon for cities with different population sizes across a country, especially for those in the developing world. Besides, commonly used inequality measures are always hindered by the conceptual simplification without accounting for human mobility in greenspace exposure assessments. To fill this knowledge gap, we leverage multi-source geospatial big data and a modified assessment framework to evaluate the inequality in urban greenspace exposure for 303 cities in China. Our findings reveal that the majority of Chinese cities are facing high inequality in greenspace exposure, with 207 cities having a Gini index larger than 0.6. Driven by the spatiotemporal variability of human distribution, the magnitude of inequality varies over different times of the day. We also find that exposure inequality is correlated with low greenspace provision with a statistical significance (p-value < 0.05). The inadequate provision may result from various factors, such as dry cold climate and urbanization patterns. Our study provides evidence and insights for central and local governments in China to implement more effective and sustainable greening programs adjusted to different local circumstances and incorporate the public participatory engagement to achieve a real balance between greenspace supply and demand for developing healthy cities.

Effects of CDK6 regulated by miR-298 on proliferation and apoptosis of thyroid cancer cells were explored. Seventy-five cases of thyroid carcinoma and adjacent tissues were collected. The expression levels of miR-298 and CDK6 mRNA in tissues and cells were detected by RT-PCR. In addition, thyroid cancer cells and human normal thyroid cells Nthy-ori3-1 were purchased, with the former transfected with miR-298-mimics, miR-298-inhibitor, miR-NC, si-CDK6, si-NC, Sh-CDK6, Sh-NC to build cell models. Then the expression levels of miR-298 and CDK6 in thyroid cancer tissues and cells were detected by qRT-PCR, and the expression of CDK6, Bax, Bcl-2 and caspase-3 by WB. CCK-8 and flow cytometry were employed to detect cell proliferation and apoptosis, and dual luciferase report was adopted to determine the relationship between miR-298 and CDK6. miR-298 was underexpressed in thyroid cancer, and CDK6 was highly expressed in thyroid cancer. Cell experiments revealed that overexpression of miR-298 or inhibition of CDK6 expression could suppress cell proliferation, promote apoptosis, and significantly increase the expression levels of Bax and caspase-3 proteins, decrease Bcl-2 protein expression, which was contrary to the biological phenotype of cells after inhibition of miR-298 or further overexpression of CDK6. Dual luciferase report confirmed that miR-298 was a targeting site of CDK6. miR-298 can inhibit the proliferation of thyroid cells and promote apoptosis of thyroid cancer cells by regulating the expression of CDK6, which is expected to be a potential target for clinical application.

In this paper, a new less-rare-earth double-stator modulated machine is proposed, where two types of permanent magnets (PM) of rare-earth NdFeB-PM and nonrare-earth ferrite-PM are skillfully integrated into a stator-partitioned modulated machine. The operating principle of the proposed machine is introduced. Considering the multioperation conditions of traction motor for electric vehicle (EV), the new machine design dimension formulas are deduced. Then, the corresponding electromagnetic performances under different driving modes are also analyzed and simulated in details. Both theoretical analysis and the FEM results show that the proposed machine has advantages in multidriving modes, which may be an interesting candidate for EV driving application.

The nature of urban space has long-drawn geographers' interest and David Harvey's conceptual framework of multiple spaces (i.e., absolute, relative, and relational) within cities has been widely adopted and developed. With its high spatial and temporal resolution, geospatial big data plays an increasingly important role in our understanding of urban structure. Taxi trajectory data is particularly useful in travel purpose estimation and allows for more granular insights into urban mobility due to the door-to-door nature of these trips. This article utilizes taxi trajectory data and explores the interaction among absolute space, relative space, and relational space in Harvey's framework using Structural Equation Modeling (SEM). Through an empirical study of Shanghai's downtown area, this paper highlights the importance of Harvey's framework in understanding cities' dynamic structure and argues for changes in urban planning and development to better coordinate land use and travel demand. We find an insignificant relationship between relative and relational space in Shanghai due to a mismatch between urban mobility and the built environment. This mismatch concentrates the transportation flow near the city's core area, transforming the polycentric structure of Shanghai's built environment in absolute space to a single-node structure in relational space. After identifying the contributing factors to this problem in Shanghai, this article suggests combining Harvey's conceptual framework of multiple spaces with geospatial big data to inform planning strategies that address the challenges of rapid urbanization.

The high speed railway (HSR) network in China has developed rapidly over the past ten years, offering a new means of travel and also regenerating and redistributing economic activities by encouraging population mobility. Using the Yangtze River Delta urban agglomeration as a case study, this paper investigates the redistribution of economic activities resulting from HSRs by developing a locally weighted regression model, geographically network weighted regression (GNWR). This GNWR is formulated in light of the current account identity in economics, and incorporates the changes in network-based travel time from HSRs and the degrees of cities, thereby offering a more appropriate method of capturing the movement of economic activities. Importantly, the coefficients in GNWR can reflect the net inflow or outflow of different cities in terms of their residents' investment and/or consumption. The results of the analysis show that HSRs have significantly changed the spatial redistribution of economic activities due to more frequent and rapid mobility. For investment activities, HSR drew the inflow to the second tier cities alongside HSR and strengthened the status of core cities; for consumption activities, HSR motivated the inflow to non-HSR cities located in the peripheral areas.

Recent studies have indicated the potential of stem cell therapy in combination with cytokines to restore the bone repair via migration and homing of stem cells to the defected area. The present study aimed to investigate the mobilization and recruitment of mesenchymal stem cells (MSCs) in response to SDF-1. Herein, the knockout rat model of the bone defect (BD) was treated with the induced membrane technique. Then, wild type Wistar rats and SDF-1-knockout rats were selected for the establishment of BD-induced membrane (BD-IM) models and bone-graft (BG) models. The number of MSCs was evaluated by flow cytometry, along with the expression pattern of the SDF-1/CXCR4 axis as well as osteogenic factors was identified by RT-qPCR and Western blot analyses. Finally, the MSC migration ability was assessed by the Transwell assay. Our data illustrated that in the induced membrane tissues, the number of MSCs among the BD-IM modeled rats was increased, whereas, a lower number was documented among BG modeled rats. Besides, we found that lentivirus-mediated over-expression of SDF-1 in BG modeled rats could activate the SDF-1/CXCR4 axis, mobilize MSCs into the defect area, and up-regulate the osteogenic proteins. Collectively, our study speculated that up-regulation of SDF-1 promotes the mobilization and migration of MSCs through the activation of the SDF-1/CXCR4 signal pathway.

The comparison of absolute geomagnetic instruments is an important component of geomagnetic observation. To promote high quality standards in geomagnetic data acquisition, the International Association of Geomagnetism and Aeronomy (IAGA) organizes an international comparison every two years. In China, this comparison is part of quality control process for geomagnetic observation data, and is organized by the Geomagnetic Network of China (GNC). In this paper, the comparison results from several years are analysed in detail, and some useful information is presented that will help to guide the observatory’s future observation work and improve data quality. In addition, the quality of the absolute observation data of GNC and IAGA is evaluated using a statistical method. This should aid scientists who use these data to understand their research results.

Objectives Recently, the role of microRNA-31-5p (miR-31-5p) in gene expression regulation has been reported in various cancers. Studies have shown that Wnt/β-catenin signaling pathway is involved in the proliferation and invasion of osteosarcoma (OS) cells. Therefore, this study aims to probe into the regulatory role of miR-31-5p targeting AXIN1 in OS cells through Wnt/β-catenin signaling pathway. Methods Firstly, microarray expression profiles were used to screen differentially expressed miRNAs associated with OS. Next, OS and normal fibrous connective tissues as well as OS cell lines were obtained for investigating the role of miR-31-5p on OS. Then, the putative binding sites between miR-31-5p and AXIN1 were predicted and verified. The regulatory effects of miR-31-5p on proliferation and invasion as well as tumorigenic potential of OS cells targeting AXIN1 were also analyzed. Besides, the relationship between miR-31-5p and Wnt/β-catenin signaling pathway was assessed by immunofluorescence staining. Results The microarray dataset GSE63939 showed that miR-31-5p and AXIN1 were involved in OS. miR-31-5p expression increased while the expression of AXIN1 decreased in OS tissues and cells. AXIN1 was identified as a target gene of miR-31-5p, intense expression of which inhibited the transcription of AXIN1. Down-regulated miR-31-5p suppressed proliferation, invasion and tumorigenicity of OS cells through promoting AXIN1. Decreased miR-31-5p activated Wnt/β-catenin signaling pathway, as reflected by increased β-catenin translocation into nuclei, through up-regulating the transcription of AXIN1. Conclusions All in all, repression of miR-31-5p targets AXIN1 to activate the Wnt/β-catenin signaling pathway, thus suppressing proliferation, invasion and tumorigenicity of OS cells.

Absolute geomagnetic measurement is very important work in geomagnetic observatories. It plays a decisive role in data quality control and instrument calibration. As modern fluxgate theodolite in absolute geomagnetic measurements has a high precision, usually with 1 second of arc, the measurement results are susceptible to external factors. The personal difference is one of these factors, and it has become an important factor that cannot be ignored in measurement results. In order to estimate the personal difference, an experiment has been designed. Six fluxgate theodolites were used and six observers who were proficient in absolute measurements were invited to this experiment. Then observers made the absolute geomagnetic measurements in turns, and the personal difference among the observers for each instrument was computed by comparing baseline values. Finally, the personal difference can be estimated by a statistical method.

A general and efficient acylative Suzuki coupling of active amides with diarylborinic acids has been achieved by using 1 mol% Pd(PCy3)2Cl2/0.6 mol% PCy3 as catalyst system taking advantage of modifiable reactivities of acyl-nitrogen bonds of amides. Both electronic and steric influences from either aryl or acyl counterparts on the coupling proved to be negligible or small. A variety of aryl ketones including sterically hindered ones could be synthesized by the coupling of diarylborinic acids in good to excellent yields. Sodium tetraarylborates could also be used as high atom-economy aryl source in the palladium-catalyzed cross-coupling with active amides.

It has been widely acknowledged that air pollution has a considerable adverse impact on people's health. Disadvantaged groups such as low-income people are often found to experience greater negative effects of environmental pollution. Thus, improving the accuracy of air pollution exposure assessment might be essential to policy-making. Recently, the neighborhood effect averaging problem (NEAP) has been identified as a specific form of possible bias when assessing individual exposure to air pollution and its health impacts. In this paper, we assessed the real-time air pollution exposure and residential-based exposure of 106 participants in a high-pollution community in Beijing, China. The study found that: (1) there are significant differences between the two assessments, (2) most participants experienced the NEAP and could lower their exposure by their daily mobility, (3) three vulnerable groups with low daily mobility and could not avoid the high pollution in their residential neighborhoods were identified as exceptions to this: low-income people who have low levels of daily mobility and limited travel outside their residential neighborhoods, blue-collar workers who spend long hours at low-end workplaces, and elderly people who face many household constraints. Public policies thus need to focus on the hidden environmental injustice revealed by the NEAP in order to improve the well-being of these environmentally vulnerable groups.

A highly efficient palladium-catalyzed acylative cross-coupling of carboxylic amides with arylboronic acids has been achieved via synergistic activation of the C(acyl)-N bond by independently modifiable activating groups. Coupling of amides features not only good functional group tolerance but also modifiable reactivities to overcome steric hindrance.

This paper describes a practical and efficient procedure that takes advantage of diarylborinic acids as a cost-effective alternative to arylboronic acids for synthesis of diarylmethanes through metal-free reductive cross-coupling with N-tosylhydrazones of aromatic aldehydes and ketones. The procedure tolerates hydroxyl, halide, amine, and allyl functionality, complementary to the transition-metal catalyzed cross-coupling techniques.

A general and efficient acylative Suzuki coupling of active amides with diarylborinic acids has been achieved by using 1 mol% Pd(PCy3)2Cl2/0.6 mol% PCy3 as catalyst system taking advantage of modifiable reactivities of acyl-nitrogen bonds of amides. Both electronic and steric influences from either aryl or acyl counterparts on the coupling proved to be negligible or small. A variety of aryl ketones including sterically hindered ones could be synthesized by the coupling of diarylborinic acids in good to excellent yields. Sodium tetraarylborates could also be used as high atom-economy aryl source in the palladium-catalyzed cross-coupling with active amides.

The improved city clustering algorithm can be used to identify urban boundaries on a digital map, and the results are a set of isolines. The relationships between the urban measurements within the variable boundaries follow allometric scaling law, which indicates spatial allometry of cities. This paper is devoted to exploring the fractal dimension proceeding from urban spatial allometry. By theoretical reasoning and empirical analysis of urban traffic network, we can derive a set of fractal dimension from the spatial allometry and reveal the basic property of the new fractal parameters. The findings are as follows. First, the fractal dimension values of traffic lines are higher than those of traffic nodes. Second, the fractal dimension values based on variable boundaries are lower than those based on the concentric circles. Conclusions can be reached that the fractal dimensions coming from spatial allometry are a type of correlation dimension rather than capacity dimension, and the relative growth rate of traffic points is greater than that of traffic nodes. This study provides new way of understanding allometry, fractals, and scaling in urban systems., 25 pages, 7 figures, 4 tables

A new highly efficient palladium-catalyzed acylative cross-coupling of carboxylic amides with arylboronic acids features not only good functional group tolerance but also modifiable reactivities to overcome steric hindrance.

As drug therapies become increasingly sophisticated, the synergistic benefits of two or more drugs are often required. In this study, we aimed at improving anti-tumor efficiency of paclitaxel (PTX)-incorporated thermo-sensitive injectable hydrogel by the synergy of burst release of doxorubicin hydrochloride (DOX⋅HCl). Thermosensitive injectable hydrogel composed of nanoparticles assembled from amphiphilic copolymer poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(e-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) was fabricated. Hydrophobic PTX and hydrophilic DOX⋅HCl were loaded simultaneously in the thermo-sensitive injectable hydrogel by a two-stage entrapment. Thermosensitive gelling behaviors of drug-loading PECT nanoparticle aqueous dispersions were studied. In vitro release profiles of PTX and DOX⋅HCl and in vivo anti-tumor effect by dual drugs from PECT hydrogel were investigated. The results showed that hydrophilic and hydrophobic drugs could be successfully entrapped in PECT hydrogel simultaneously without affecting its thermo-sensitive behavior. In vitro release profiles demonstrated the burst release of DOX⋅HCl and the sustained release of PTX. Anti-tumor effect was improved by a fast and tense attack caused by the burst release of hydrophilic DOX⋅HCl from hydrogel, which was continued by the sequent sustained release of PTX-incorporated nanoparticles and remnant DOX⋅HCl. Unintentionally, entrapped in PECT hydrogel, hydrophilic DOX⋅HCl was observed to have a sustained releasing pattern in vitro and in vivo.

This paper describes a practical and efficient procedure that takes advantage of diarylborinic acids as a cost-effective alternative to arylboronic acids for synthesis of diarylmethanes through metal-free reductive cross-coupling with N-tosylhydrazones of aromatic aldehydes and ketones. The procedure tolerates hydroxyl, halide, amine, and allyl functionality, complementary to the transition-metal catalyzed cross-coupling techniques.

A one-dimensional linear inverse heat conduction problem is studied in this paper. This ill-posed problem is replaced by the perturbed problem with a non-localized boundary condition. After the derivation of its closed-form analytical solution, the calculation error can be determined by the comparison between the numerical and exact solutions.