Analysis and prediction of compressive and split-tensile strength of secondary steel fiber reinforced concrete based on RBF fuzzy neural network model.

Accurate analysis of the strength of steel-fiber-reinforced concrete (SFRC) is important for ensuring construction quality and safety. Cube compression and splitting tensile tests of steel fiber with different varieties, lengths, and dosages were performed, and the effects of different varieties, lengths, and dosages on the compressive and splitting properties of secondary concrete were obtained. It was determined that the compression and splitting strengths of concrete could be effectively improved by the addition of end-hooked and milled steel fibers. The compressive and splitting strengths of concrete can be enhanced by increasing the fiber length and content. However, concrete also exhibits obvious uncertainty owing to the comprehensive influence of steel fiber variety, fiber length, and fiber content. In order to solve this engineering uncertainty, the traditional RBF neural network is improved by using central value and weight learning strategy especially. On this basis, the RBF fuzzy neural network prediction model of the strength of secondary steel fiber-reinforced concrete was innovatively established with the type, length and content of steel fiber as input information and the compressive strength and splitting tensile strength as output information. In order to further verify the engineering reliability of the prediction model, the compressive strength and splitting tensile strength of steel fiber reinforced concrete with rock anchor beams are predicted by the prediction model. The results show that the convergence rate of the prediction model is increased by 15%, and the error between the predicted value and the measured value is less than 10%, which is more efficient and accurate than the traditional one. Additionally, the improved model algorithm is efficient and reasonable, providing technical support for the safe construction of large-volume steel fiber concrete projects, such as rock anchor beams. The fuzzy random method can also be applied to similar engineering fields.

Discoidin domain receptor 2 signaling through PIK3C2α in fibroblasts promotes lung fibrosis.

Pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), portends significant morbidity and mortality, and current therapeutic options are suboptimal. We have previously shown that type I collagen signaling through discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase expressed by fibroblasts, is critical for the regulation of fibroblast apoptosis and progressive fibrosis. However, the downstream signaling pathways for DDR2 remain poorly defined and could also be attractive potential targets for therapy. A recent phosphoproteomic approach indicated that PIK3C2α, a poorly studied member of the PI3 kinase family, could be a downstream mediator of DDR2 signaling. We hypothesized that collagen I/DDR2 signaling through PIK3C2α regulates fibroblast activity during progressive fibrosis. To test this hypothesis, we found that primary murine fibroblasts and IPF-derived fibroblasts stimulated with endogenous or exogenous type I collagen led to the formation of a DDR2/PIK3C2α complex, resulting in phosphorylation of PIK3C2α. Fibroblasts treated with an inhibitor of PIK3C2α or with deletion of PIK3C2α had fewer markers of activation after stimulation with TGFß and more apoptosis after stimulation with a Fas-activating antibody. Finally, mice with fibroblast-specific deletion of PIK3C2α had less fibrosis after bleomycin treatment than did littermate control mice with intact expression of PIK3Cα. Collectively, these data support the notion that collagen/DDR2/PIK3C2α signaling is critical for fibroblast function during progressive fibrosis, making this pathway a potential target for antifibrotic therapy. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Exponential synchronization of delayed coupled neural networks with delay-compensatory impulsive control.

This paper studies the exponential synchronization problem for a class of delayed coupled neural networks with delay-compensatory impulsive control. A Razumikhin-type inequality involving some destabilizing delayed impulse gains and a new idea of delay-compensatory that shows two critical roles for system stability are presented, respectively. Based on the constructed inequality and the presented delay-compensatory idea, sufficient stability and synchronization criteria for globally exponential synchronization (GES) of coupled neural networks (CNNs) are presented. Compared with existing results, the uniqueness of the presented results lies in that impulse delays can be fetched and integrated to compensate for instantaneous unstable impulse dynamics caused by destabilizing gains. Moreover, constraints between system delay and impulsive delay are relaxed, and the interval of impulses no longer constrains the system delay. Comparisons and a practical application are given to demonstrate the superior performance of the presented novel control methods.

CD36/Lyn kinase interactions within macrophages promotes pulmonary fibrosis in response to oxidized phospholipid.

Recent data from human studies and animal models have established roles for type II alveolar epithelial cell (AEC2) injury/apoptosis and monocyte/macrophage accumulation and activation in progressive lung fibrosis. Although the link between these processes is not well defined, we have previously shown that CD36-mediated uptake of apoptotic AEC2s by lung macrophages is sufficient to drive fibrosis. Importantly, apoptotic AEC2s are rich in oxidized phospholipids (oxPL), and amongst its multiple functions, CD36 serves as a scavenger receptor for oxPL. Recent studies have established a role for oxPLs in alveolar scarring, and we hypothesized that uptake and accrual of oxPL by CD36 would cause a macrophage phenotypic change that promotes fibrosis. To test this hypothesis, we treated wild-type and CD36-null mice with the oxPL derivative oxidized phosphocholine (POVPC) and found that CD36-null mice were protected from oxPL-induced scarring. Compared to WT mice, fewer macrophages accumulated in the lungs of CD36-null animals, and the macrophages exhibited a decreased accumulation of intracellular oxidized lipid. Importantly, the attenuated accrual of oxPL in CD36-null macrophages was associated with diminished expression of the profibrotic mediator, TGFß. Finally, the pathway linking oxPL uptake and TGFß expression was found to require CD36-mediated activation of Lyn kinase. Together, these observations elucidate a causal pathway that connects AEC2 injury with lung macrophage activation via CD36-mediated uptake of oxPL and suggest several potential therapeutic targets.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

Inhibition of discoidin domain receptor 2 reveals kinase-dependent and kinase-independent functions in regulating fibroblast activity.

Progressive pulmonary fibrosis is a devastating condition and current treatment is suboptimal. There has been considerable interest in the role of tyrosine kinase signaling as mediators of pro- and antifibrotic processes. Nintedanib is a nonspecific tyrosine kinase that has been shown to have therapeutic benefit in lung fibrosis. However, the precise mechanism of action remains unclear because nintedanib inhibits several tyrosine kinases, which are often expressed on multiple cell types with different activities during fibrosis. Discoidin domain receptor 2 (DDR2) has been suggested as a potential target of nintedanib. DDR2 is a receptor tyrosine kinase that is activated by fibrillar collagens such as type I collagen. DDR2 is primarily expressed by fibroblasts. The effectiveness of specifically targeting DDR2 signaling during fibrosis remains undefined. In the present study, we show that nintedanib acts as a direct and indirect inhibitor of DDR2. We then utilize a novel allosteric inhibitor of DDR2, WRG-28, which blocks ligand binding and activation of DDR2. We find that WRG-28 augments fibroblast apoptosis and attenuates fibrosis. Finally, we show that fibroblast type I collagen autocrine signaling is regulated by DDR2 through both kinase-dependent and kinase-independent functions of DDR2. These findings highlight the importance of type I collagen autocrine signaling by fibroblasts during fibrosis and demonstrate that DDR2 has a central role in this pathway making it a potential therapeutic target.NEW & NOTEWORTHY Type I collagen is a major component of fibrosis and can signal through cell surface receptors such as discoidin domain receptor 2 (DDR2). DDR2 activation can lead to further collagen deposition by fibroblasts setting up a profibrotic positive feedback loop. In this report, we find that inhibition of DDR2 with nintedanib or a specific DDR2 inhibitor, WRG-28, can disrupt this cycle and prevent fibrosis through augmented fibroblast apoptosis and inhibited activation.

Catheterization Before Transperineal Ultrasound-guided Prostate Biopsy and the Risk of Urethrorrhagia.

OBJECTIVE: To investigate the efficacy of catheterization before transperineal ultrasound-guided prostate biopsy in reducing risk of urethrorrhagia. Currently, transperineal ultrasound-guided prostate biopsy (TPPB) is one of the most commonly used measures to help diagnose prostate cancer. However, whether the retention of catheterization before transperineal ultrasound-guided prostate biopsy is associated with the reduced risk of urethrorrhagia remains uncertain. METHODS: A cohort study was conducted in our hospital from January 2021 to September 2021. This study included 93 patients who participated in transperineal ultrasound-guided prostate biopsy. We compared the risk of urethrorrhagia in patients who underwent indwelling catheterization before biopsy and those who did that after biopsy, and performed an unadjusted analysis. We also analyzed the use of related confounding factors to limit the cohort of men, and applied propensity-score adjustment to control potential confounders. Analyses that restricted the cohort men with the related confounding factors and that used propensity-score adjustment to control for potential confounders. RESULTS: A total of 93 men were recruited in the cohort study, and the numbers of patients in group 1 and group 2 were 64 and 29, respectively. There were 34 patients (53.1%) of urethrorrhagia in group 1, and 22 patients (75.8%) of urethrorrhagia in group 2. This was a significant difference between the 2 groups (P = .008). After adjusting for correlative factors, the preoperative catheterization is still a protective factor for postoperative urethrorrhagia through multivariate multiple piecewise linear regression analysis. CONCLUSION: The result of this cohort study suggested that preoperative catheterization can significantly reduce the risk of urethrorrhagia.

Detoxification Mechanism of Combined Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta in Regulating Cardiac Metabolic Enzyme CYP2J3 / 中国实验方剂学杂志

ObjectiveTo investigate the detoxification mechanism of Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta， and their effective components ellagic acid， liquiritin and aconitine based on cardiac cytochrome P450 （CYP450） system. MethodIn in vivo experiments， rats were randomly divided into control group， prepared Aconiti Kusnezoffii Radix Cocta group （0.25 g·kg-1）， Chebulae Fructus group （0.252 g·kg-1）， Glycyrrhizae Radix et Rhizoma group （0.25 g·kg-1） and combination group （0.25 g·kg-1 Chebulae Fructus+0.25 g·kg-1 Glycyrrhizae Radix et Rhizoma+0.25 g·kg-1 prepared Aconiti Kusnezoffii Radix Cocta， with prepared Aconiti Kusnezoffii Radix Cocta as standard）. After 8 days of administration， creatine kinase （CK） and lactate dehydrogenase （LDH） in rats were detected to observe the pathological changes of heart tissue. Real-time PCR and Western blot were performed to detect the mRNA and protein expressions of CYP2J3， respectively. In in vitro experiments， control group， aconitine group， ellagic acid group， liquiritin group and combination group （aconitine+ellagic acid+liquiritin） were set， and their effects on cell number， DNA content， reactive oxygen species （ROS） and mitochondrial membrane potential （MMP） were detected by high content analysis. The changes in the mRNA and protein expressions of CYP2J3 were also observed. ResultIn vivo experiments， compared with the control group， the prepared Aconiti Kusnezoffii Radix Cocta group had increased CK and LDH in serum （P<0.05， P<0.01）， while the combination group had decreased activities of CK and LDH. Additionally， pathological staining results showed that Chebulae Fructus and Glycyrrhizae Radix et Rhizoma reduced the cardiac toxicity caused by prepared Aconiti Kusnezoffii Radix Cocta. Real-time PCR found that compared with the control group， prepared Aconiti Kusnezoffii Radix Cocta down-regulated the mRNA level of CYP2J3 （P<0.05）， while up-regulated that expression when used in combination with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma （P<0.01）. The protein and mRNA translation levels were basically consistent. In vitro experiments， high content analysis revealed that there was a decrease in the cell number， DNA content and MMP fluorescence value of the aconitine group （P<0.01） and the combination group （P<0.05， P<0.01）， and the fluorescence value of the combination group was higher than that of the aconitine group. Moreover， aconitine down-regulated the mRNA level of CYP2J3 （P<0.05）， but the down-regulating ability of aconitine was reversed in the combination group （P<0.05）. ConclusionThe detoxification mechanism of combined Chebulae Fructus， Glycyrrhizae Radix et Rhizoma and prepared Aconiti Kusnezoffii Radix Cocta is mainly that the combination of ellagic acid， liquiritin and aconitine can up-regulate the expression of CYP2J3， and promote the metabolism of arachidonic acid （AA） to produce epoxyeicosatrienoic acids （EETs）， thus reducing the cardiac toxicity， and this effect may start from the transcriptional link.

Study on the effects and mechanism of Guiling Gao on the activity state of rats with damp-heat syndrome / 国际中医中药杂志

Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.

Effects of circadian rhythm on the development of dental hard tissues / 中华口腔医学杂志

Circadian rhythm is regulated by circadian clock, which is formed by the body response to external cyclic stimuli through the endogenous circadian clock. Circadian rhythm disturbance is closely related to the risks of a variety of diseases, and its impact on oral health cannot be ignored. Exploring the relationship and related molecular mechanism between circadian rhythm and dental hard tissues development are helpful to deeply understand the pathogenesis of developmental defects on these tissues, which could provide a theoretical basis for prevention and treatment on disorders of dental hard tissues. In order to provide guidance for the disease prevention and treatment, based on the summarization of current research progress, this paper focuses on the involvement of biorhythm in the development of tooth hard tissues as well as the disturbance of circadian rhythm on the formation of enamel and dentin, and analyzes the related regulating mechanism of circadian rhythm and genes during the development of tooth hard tissues.

Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction / 中国中药杂志

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Association between anesthesia technique and complications after hip surgery in the elderly population.

BACKGROUND: Spinal anesthesia is superior to general anesthesia for postoperative recovery in older patients (≥ 65 age). However, evidence for this is lacking. AIM: To evaluate the effect of anesthesia on postoperative complications in older patients undergoing hip surgery. METHODS: This is a retrospective, propensity score-matched, cohort study. Patients ≥ 65-years-old who underwent hip surgery at the Traditional Chinese Medicine of Guangdong Provincial Hospital in China from October 2016 to June 2020 were included. The operative methods were femoral fracture's internal fixation and hip replacement. The orthopedic doctors in different hospitals of our group have varied requirements for patients' out-of-bed time after surgery. Therefore, spinal anesthesia or general anesthesia was selected according to the requirements of the orthopedic doctors. The primary outcome of this study was complications during the hospitalization of the postoperative patient. The length of hospital stay, postoperative blood transfusion, routine blood analysis, renal function, coagulation function, and inflammatory correlations were secondary outcomes. Propensity score matching (PSM) was performed utilizing logistic regression. RESULTS: Among the 864 patients identified from the electronic medical record data database, we screened out those with incomplete medical record data. After PSM of the baseline values of the two groups of patients, data of 309 patients (206 patients in spinal anesthesia group and 103 patients in general anesthesia) were utilized in this study. 67/309 patients had complications, including postoperative limb dysfunction, pulmonary infection, delirium, lower extremity venous thrombosis, and shock. The incidence of complications was not related to anesthesia methods (P > 0.05), but the levels of D-Dimer (P = 0.017), fibrinogen (P = 0.005), and high-sensitivity C-reactive protein (hsCRP) (P = 0.002) in the spinal anesthesia group were significantly higher than those in the general anesthesia group. CONCLUSION: Anesthesia technology is not a risk factor for postoperative complications of hip surgery. The levels of D-Dimer and hsCRP were higher in the spinal anesthesia group.

Hydrochemical patterns indicating hydrological processes with the background of changing climatic and environmental conditions in China: a review.

In the background of global climate and environmental change, the hydrochemical characteristics of water bodies present significant instability to all regions, including humid, arid, and alpine ones. There are two main reasons for this: (1) climate change has altered the temporal and spatial distribution of precipitation, and climate warming intensified the mutual transformation of water bodies. The temperature in China increased by 0.29 °C/10a from 1951 to 2018. For different regions, whether the alpine region (0.37 °C/10a, P < 0.05), the arid region (0.278 °C/10a, P < 0.05), or the humid region (0.168 °C/10a, P < 0.05), there was a significant increasing trend (P < 0.05) from 1951 to 2018. Thus, the characteristics of water recharge sources and the hydrological processes and hydrochemical characteristics of water bodies are affected. Increase in precipitation increases the input sources for water transformation, intensifying the transformation of water bodies. (2) In the context of climate and environmental change, human activities and the local environment are seriously affecting the transformation of various water bodies and hydrochemical ion sources. The comprehensive effects of various physical and geographical conditions, geological structure, lithology and transformation, and recharge of various water bodies affect the hydrochemical characteristics of water bodies in China. The differences in the type of water bodies showed that the hydrochemical process of water bodies was more complex, although there was a hydraulic connection between precipitation, river water, lake water, and groundwater. This provides a new idea for the future study of hydrochemical characteristics and hydrology.

Bulk phosphorous deposition at four typical land use sites in Southwest China.

Whilst ongoing increases in the deposition of atmospheric nitrogen (N) in China have attracted a lot of attention, to date there has been little research on phosphorus (P) deposition. In this study, we quantified inorganic P (PO43-), dissolved organic P (DOP) and total P (TP) in bulk deposition at four sites in the Sichuan Basin, Southwest China. Chengdu (CD), Shifang (SF), Yanting (YT), and Gongga (GG). They represent the land use categories urban, suburban, agricultural and forest, respectively, during 2008-2018 at CD and YT, 2015-2018 at SF, and 2007-2014 at GG. Annual average TP concentrations (deposition rates) were 0.07 (0.61), 0.49 (3.22), 0.17 (1.07) and 0.01 (0.20) mg L-1 (kg ha-1 yr-1), at CD, SF, YT and GG, respectively. The TP concentrations at YT and GG showed significant increasing trends over the years, with very little change at CD and a decline at SF because of the implementation of environmental control measures. Average PO43- to DOP ratios were 0.65, 0.95, 0.82 and 0.81 at CD, SF, YT and GG, respectively, indicating that DOP accounts for a higher proportion at the urban site, and dominated by combustion sources. Bulk P deposition showed higher deposition rates in summer and lower in winter. These results highlight the importance of long term monitoring in detecting spatial and temporal changing trends of the chemical composition, so as to implement effective policies to eliminate air pollution, especially for Southwest China, where there is limited research on atmospheric P deposition.

Megastigmanes from an aqueous extract of Uncaria rhynchophylla / 药学学报

Five new megastigmanes (1-5) were isolated from a decoction of Uncaria rhynchophylla by separation techniques of column chromatography using a combination of multiple stationary phases, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40F, and reversed phase HPLC. Their structures were characterized by spectroscopic data analysis of HR-ESI-MS, NMR, and CD, in combination with Mosher's mothed as well as ECD and NMR calculations. The new compounds were named uncarphyllonone A (1), uncarphyllonols A (2) and B (3), and uncarphabscisic acids A (4) and B (5). Although the structures of 3 and 4 were previously reported, the reported NMR spectroscopic data were incorrect or do not support the assigned structures in literatures. This is also the first report of discovery of new megastigmane natural products from the Uncaria genus.

Ferroptosis of airway epithelial cells in asthma: current and future / 药学学报

Ferroptosis is a novel cell death mode proposed in recent years, which is characterized by intracellular iron-dependent lipid peroxidation. Its mechanisms include lipid peroxidation, iron accumulation and the imbalance of antioxidant system. The crosstalk between ferroptosis and asthma is gradually deepening. Elucidating the specific mechanism of ferroptosis in regulating asthma is helpful to broaden the understanding of the pathology of asthma. This paper expounds the role of ferroptosis in airway epithelial cells in the occurrence and development of asthma from three perspectives: lipid peroxidation, iron accumulation and the imbalance of antioxidant system, hoping to find new targets and strategies for asthma treatment.

Progress of discovery of molecular glues from natural products and their derivatives / 药学学报

Molecular glues are a class of small molecules that induce the formation of protein-protein interactions to confer new biological function or therapeutic effects. As a unique pharmacological modality, molecular glues could target proteins without druggable binding pockets. It exhibits a variety of functions, including regulating signal transduction, stabilization or degradation of targeted proteins, through sticking different proteins together. This review will summarize the development and current status of molecular glues derived from natural products and analogs by illustrating the discovery and interaction mechanism. We hope to present a systematic view, provide valuable clues for researchers and encourage them to explore more efficient and rational molecular glue discovery strategies.

Effect of Curcumin on Apoptosis of Acute T-Lymphoblastic Leukemia Cells induced by UMI-77 and Its Related Mechanism / 中国实验血液学杂志

AbstractObjective: To explore the effect and mechanism of curcumin on human T-cell acute lymphoblastic leukemia (T-ALL) cell apoptosis induced by Mcl-1 small molecule inhibitors UMI-77.@*METHODS@#T-ALL cell line Molt-4 was cultured, and the cells were treated with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77 for 24 h. The MTT method was used to detect the cell survival rate after different treatment; According to the results of curcumin and UMI-77, the experimental settings were divided into control group, curcumin group (20 μmol/L curcumin treated cells), UMI-77 group (15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells) and curcumin+ UMI-77 group (20 μmol/L curcumin and 15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells), MTT method was used to detect cell proliferation inhibition rate, Annexin V-FITC/PI double staining method and TUNEL staining were used to detect cell apoptosis, DCFH-DA probe was used to detect cell reactive oxygen species, JC-1 fluorescent probe was used to detect mitochondrial membrane potential, Western blot was used to detect the expression levels of apoptosis-related proteins and Notch1 signaling pathway-related proteins.@*RESULTS@#After the treatment of Molt-4 cells with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77, the cell survival rate was decreased (P<0.05); Compared with the control group, the cell proliferation inhibition rate of the curcumin group and the UMI-77 group were increased, the apoptosis rate of cell was increased, the level of ROS was increased, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, and the protein expression of Bcl-2 was reduced (P<0.05); Compared with the curcumin group or UMI-77 group, the cell proliferation inhibition rate and apoptosis rate of the curcumin+UMI-77 group were further increased, and the level of ROS was increased. At the same time, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, the protein expression of Bcl-2 was reduced (P<0.05); In addition, the mitochondrial membrane potential of the cells after curcumin treatment was decreased, and the proteins expression of Notch1 and HES1 were reduced (P<0.05).@*CONCLUSION@#Curcumin can enhance the apoptosis of T-ALL cells induced by Mcl-1 small molecule inhibitor UMI-77 by reducing the mitochondrial membrane potential, the mechanism may be related to the inhibition of Notch1 signaling pathway.

Interference of P2X4 receptor expression in tumor-associated macrophages suppresses migration and invasion of glioma cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of interference of P2X4 receptor expression in tumor-associated macrophages (TAMs) on invasion and migration of glioma cells.@*METHODS@#C57BL/6 mouse models bearing gliomas in the caudate nucleus were examined for glioma pathology with HE staining and expressions of Iba-1 and P2X4 receptor with immunofluorescence assay. RAW264.7 cells were induced into TAMs using conditioned medium from GL261 cells, and the changes in mRNA expressions of macrophage polarization-related markers and the mRNA and protein expressions of P2X4 receptor were detected with RT-qPCR and Western blotting. The effect of siRNA-mediated P2X4 interference on IL-1β and IL-18 mRNA and protein expressions in the TAMs was detected with RT-qPCR and Western blotting. GL261 cells were cultured in the conditioned medium from the transfected TAMs, and the invasion and migration abilities of the cells were assessed with Transwell invasion and migration experiment.@*RESULTS@#The glioma tissues from the tumor-bearing mice showed a significantly greater number of Iba-1-positive cells, where an obviously increased P2X4 receptor expression was detected (P=0.001), than the brain tissues of the control mice (P < 0.001). The M2 macrophage markers (Arg-1 and IL-10) and M1 macrophage markers (iNOS and TNF-α) were both significantly up-regulated in the TAMs derived from RAW264.7 cells (all P < 0.01), but the up-regulation of the M2 macrophage markers was more prominent; the expression levels of P2X4 receptor protein and mRNA were both increased in the TAMs (P < 0.05). Interference of P2X4 receptor expression significantly lowered the mRNA(P < 0.01)and protein (P < 0.01, P < 0.05)expression levels of IL-1β and IL-18 in the TAMs and obviously inhibited the ability of the TAMs to promote invasion and migration of the glioma cells (P < 0.05).@*CONCLUSION@#Interference of P2X4 receptor in the TAMs suppresses the migration and invasion of glioma cells possibly by lowering the expressions of IL-1β and IL-18.