Design, Synthesis and Biological Evaluation of Novel Phenyl-Substituted Naphthoic Acid Ethyl Ester Derivatives as Strigolactone Receptor Inhibitor.

Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.

Long-term outcomes of endoscopic papillary large-balloon dilation (12-15 mm) with or without limited sphincterotomy for removal of bile duct stones.

BACKGROUND: Limited endoscopic sphincterotomy with large balloon dilation (ES-LBD) and endoscopic papillary large-balloon dilation (EPLBD) have been proven safe and effective for removal of bile duct stones. However, the long-term outcomes are not clear. The aim of this study was to assess the long-term outcomes of EPLBD (12-15 mm) with or without limited sphincterotomy for removal of common bile duct (CBD) stones. METHODS: Patients with EPLBD or ES-LBD referred for the removal of bile-duct stones between June 2008 and August 2020 were retrospectively reviewed. Complete stone clearance, endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events, and late biliary complications during long-term follow-up were analyzed. RESULTS: Basic patient characteristics were not significantly different between the groups that underwent EPLBD (n = 168) and ES-LBD (n = 57). EPLBD compared with ES-LBD resulted in similar outcomes in terms of overall successful stone removal (99.4% vs. 100%, P = 1.00) and ERCP-related adverse events (7.7% vs. 5.3%, P = 0.77). The mean duration of the follow-up were 113.6 months and 106.7 months for patients with EPLBD and ES-LBD, respectively (P = 0.13). There was no significant difference between EPLBD and ES-LBD in the incidence of stone recurrence [20 (11.9%) vs. 9 (15.8%); P = 0.49]. Multivariate analysis showed that a diameter of CBD ≥ 15 mm (OR = 3.001; 95% CI: 1.357-6.640; P = 0.007) was an independent risk factor for stone recurrence. CONCLUSIONS: The application of a large balloon (12-15 mm) via EPLBD is an effective and safe alternative to ES-LBD for extraction of large CBD stones. Endoscopic sphincterotomy prior to EPLBD may be unnecessary. A diameter of CBD ≥ 15 mm is a risk factor of stone recurrence.

Visuospatial or verbal-spatial codes? The different effect of two secondary tasks on the power-space associations during a semantic categorizing task.

The power-space associations have been extensively studied as a possible way to reveal the nature of concept representations, while the visuospatial and verbal-spatial codes are two primary explanations for the phenomenon. In two experiments, we imposed either a visuospatial or a verbal secondary task during the semantic categorizing of power words to examine their respective roles. The results showed that retaining a letter but not a location concurrently interfered with the power-space association. The results suggested that the verbal-spatial codes might play a more fundamental role than the visuospatial codes in the power-space associations during the semantic categorizing of power words.

A DRL-based online VM scheduler for cost optimization in cloud brokers.

The virtual machine (VM) scheduling problem in cloud brokers that support cloud bursting is fraught with uncertainty due to the on-demand nature of Infrastructure as a Service (IaaS) VMs. Until a VM request is received, the scheduler does not know in advance when it will arrive or what configurations it demands. Even when a VM request is received, the scheduler does not know when the VM's lifecycle expires. Existing studies begin to use deep reinforcement learning (DRL) to solve such scheduling problems. However, they do not address how to guarantee the QoS of user requests. In this paper, we investigate a cost optimization problem for online VM scheduling in cloud brokers for cloud bursting to minimize the cost spent on public clouds while satisfying specified QoS restrictions. We propose DeepBS, a DRL-based online VM scheduler in a cloud broker which learns from experience to adaptively improve scheduling strategies in environments with non-smooth and uncertain user requests. We evaluate the performance of DeepBS under two request arrival patterns which are respectively based on Google and Alibaba cluster traces, and the experiments show that DeepBS has a significant advantage over other benchmark algorithms in terms of cost optimization.

Cadmium inhibits signal transducer and activator of transcription 6 leading to pancreatic ß cell apoptosis.

The toxic heavy metal cadmium has been proven to cause pancreatic dysfunction and lead to the development of DM. However, the underlying mechanisms have not been completely elucidated. Here, we investigated the effects of cadmium on the pancreatic ß cell line MIN6 and explored the underlying mechanisms. The Cell Counting Kit-8 (CCK8) assay and flow cytometry were used to determine cell viability and apoptosis in MIN6 cells. The expression levels of signal transducer and activator of transcription 6 (STAT6) were assessed by western blotting. We further assessed the effects of cadmium on the function of pancreatic ß cells under high glucose levels using enzyme-linked immunosorbent assay (ELISA) and western blotting. Insulin secretion and expression were decreased by cadmium in MIN6 cells. In addition, cadmium suppressed cell viability and promoted apoptosis of MIN6 cells, downregulated insulin secretion and genesis of MIN6 cells under high glucose conditions, while inhibiting STAT6. Furthermore, after treatment with IL-4, the activator of STAT6, the MIN6 cell viability suppression and apoptosis promotion effect caused by cadmium were blocked. In conclusion, cadmium inhibits pancreatic ß cell MIN6 growth by regulating the activation of STAT6. Our findings reveal a new mechanism of cadmium toxicity in pancreatic ß cells.

Metabolic syndrome and its components are associated with thyroid volume in adolescents.

OBJECTIVE: To explore the association between metabolic syndrome (MetS) and its component and thyroid volume in Chinese adolescents, and to compare the detection rate of MetS under the three different diagnostic criteria. METHODS: A total of 1097 school students (610 males and 487 females, ages 12-15 years) were enrolled. All the participants underwent physical examination, biochemical test, and thyroid gland ultrasonography. The thyroid volume of normal, overweight and obese group was compared. We also analyzed the association between the number of MetS components and thyroid volume. Linear and multiple linear regression were applied to explore the association between metabolic parameters and thyroid volume. RESULTS: The thyroid volume of the males in overweight (t = 3.784, P < 0.001) and obese group (t = 5.068, P < 0.001) was significantly larger than that in normal group; the thyroid volume of the females in overweight group (t = 4.627,P < 0.001) was significantly larger than that of normal group. As the number of MetS components increased, the thyroid volume also increased significantly (F = 10.64, P < 0.01). Height, weight, body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and triglyceride were all positively associated with thyroid volume in the adolescents (P all < 0.001). Meanwhile, there was a negative association between high-density lipoprotein cholesterol (HDL-C) and thyroid volume (P < 0.001). According to multiple linear regression, waist circumference (ß = 0.029, 95 %CI: 0.015 ~ 0.042; P < 0.01) and waist height ratio (ß = 3.317, 95 %CI: 1.661 ~ 4.973; P < 0.01) were predict factors of thyroid volume. No statistical difference was found in the detection rates of metabolic syndrome under the three diagnostic criteria. CONCLUSIONS: Overweight, obesity and metabolic syndrome was associated with adolescent thyroid volume. Central obesity may be an independent risk factor for thyroid enlargement in adolescents.

Prevalence and Factors Associated with Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children.

BACKGROUND: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). AIM: To assess the prevalence and factors associated with post-ERCP pancreatitis (PEP) in a Chinese pediatric population. METHODS: Sixty-six children who underwent ERCP between March 2018 and March 2019 at Shanghai Children's Medical Center were retrospectively recruited for the study. Clinical data, including demographics, indications, comorbidities, and procedural data, were reviewed to identify the prevalence and factors associated with PEP. RESULTS: Ninety-two ERCPs were performed on 66 pediatric patients aged from 8 months to 14 years. The indications for ERCP were chronic pancreatitis (49, 53.2%), pancreaticobiliary maljunction (19, 20.7%), pancreas divisum (19, 20.7%), and pancreatic pseudocyst (5, 5.4%). All ERCPs were performed for therapeutic purposes. PEP was identified in 19 (20.7%) patients; there were ten mild cases, eight moderate cases, and one severe case. The univariate analysis revealed that a history of chronic pancreatitis was negatively associated with PEP (P = 0.033), and sphincterotomy was positively associated with PEP (P = 0.01). The multivariate analysis showed that sphincterotomy was a risk factor for PEP (P = 0.017, OR 4.17; 95% CI, 1.29, 13.54). CONCLUSIONS: Our data revealed a high prevalence of PEP in a Chinese pediatric population. Chronic pancreatitis was a protective factor, and sphincterotomy was a risk factor for PEP development.

A technique for registering digital dental casts onto cone beam computed tomography scans with excessive metallic artifacts.

This article describes a method of integrating digital dental casts into cone beam computed tomography (CBCT) scans in virtual implant planning in situations with an excessive number of metal artifacts. This technique requires the use of a prefabricated registration tray to provide a common landmark; is noninvasive, minimally time-consuming, and cost-effective; and requires only a single registration and minimal exposure to radiation.

Expression profiling of long noncoding RNAs associated with vasculogenic mimicry in osteosarcoma.

Osteosarcoma (OS) is the most common highly malignant bone tumor in teens. Vasculogenic mimicry (VM) is defined as de novo extracellular matrix-rich vascular-like networks formed by highly aggressive tumor cells. We previously reported the presence of VM and it is an unfavorable prognostic factor in OS patients. Long noncoding RNAs (lncRNAs) are aberrantly expressed in OS and involved in cancer cell VM. However, lncRNAs in VM formation of OS have not been investigated. We, therefore, profiled the expression of lncRNAs in highly aggressive OS cell line 143B compared with its parental poorly aggressive cell line HOS. The differentially expressed (DE) lncRNAs and messenger RNA (mRNAs) were subjected to constructed lncRNA-mRNA coexpressed network. The top-ranked hub gene lncRNA n340532 knockdown 143B cells were used for in vitro and in vivo VM assays. The annotation of DE lncRNAs was performed according to the coexpressed mRNAs by Gene Ontology and pathway analysis. A total of 1360 DE lncRNAs and 1353 DE mRNAs were screened out. lncRNA MALAT1 and FTX, which have known functions related to VM formation and tumorigenesis were identified in our data. The coexpression network composed of 226 lncRNAs and 118 mRNAs in which lncRNA n340532 had the highest degree number. lncRNA n340532 knockdown reduced VM formation in vitro. The suppression of n340532 also exhibited potent anti-VM and antimetastasis effect in vivo, suggesting its potential role in OS VM and metastasis. Furthermore, n340532 coexpressed with 10 upregulation mRNAs and 3 downregulation mRNAs. The enriched transforming growth factor-ß signaling pathway, angiogenesis and so forth were targeted by those coexpressed mRNAs, implying n340532 may facilitate VM formation in OS through these pathways and gene functions. Our findings provide evidence for the potential role of lncRNAs in VM formation of OS that could be used in the clinic for anti-VM therapy in OS.

Research on the Actuation Performance of 2D-Orthotropic Piezoelectric Composite Materials Linear Phased Array Transducer.

Ultrasonic linear phased array actuator for electric-acoustic conversion is the key component of the ultrasonic phased array test system. Focusing on the existing deficiency of using phased array ultrasonic testing technology into complex engineering structure, using the 2D orthotropic piezoelectric composite materials (2D-OPCM) into the research of linear phased array actuator can achieve orientable exciting. The single OPCM element and its array actuator was designed and their mechanical properties of focusing were tested by experiment. The experimental results show that 2D-OPCM ultrasound phased array actuator can achieve precise phased array focusing and deflection, which might be of great promising in the nondestructive evaluation engineering application.

Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells.

Neutral ceramidase (NCDase) is a class of ceramidases, a key enzyme in ceramide degradation. Recently, it was observed that NCDase activity was suppressed by saturated fatty acids to increase ceramide content in rat muscle. However, little is known about its changes in activity and roles in palmitate (Palm)-induced lipotoxicity in pancreatic ß cells. Here, we demonstrated that Palm treatment significantly down-regulated NCDase activity, mRNA and protein levels in rat INS-1 cells. In addition, Palm caused a significant accumulation of ceramide, while SPH level remained unchanged, suggesting that inhibition of NCDase activity led to no change of SPH level after treatment with Palm for 24 h. Furthermore, NCDase overexpression significantly reduced Palm-induced apoptosis in INS-1 cells. Conversely, NCDase siRNA knockdown markedly exacerbated Palm-induced apoptosis. In conclusion, Palm treatment suppressed the activity of NCDase and down-regulated its mRNA and protein expression. Furthermore, NCDase inhibition was involved in Palm-induced apoptosis by blocking ceramide degradation in INS-1 cells.

Design, Synthesis, and Bioactivities of N-Heterocyclic Ureas as Strigolactone Response Antagonists against Parasitic-Weed Seed Germination.

The pernicious parasitism exhibited by root parasitic weeds such as Orobanche and Striga poses substantial peril to agricultural productivity and global food security. This deleterious phenomenon hinges upon the targeted induction of the signaling molecule strigolactones (SLs). Consequently, the identification of prospective SL antagonists holds significant promise in the realm of mitigating the infection of these pernicious weeds. In this study, we synthesized and characterized D12 based on a potent SL antagonist KK094. In vivo assay results demonstrated that D12 remarkably impedes the germination of Phelipanche aegyptiaca and Striga asiatica seeds, while also alleviating the inhibitory consequence of the SL analogue GR24 on hypocotyl elongation in Arabidopsis thaliana. The docking study and ITC assay indicated that D12 can interact strongly with the SL receptor protein, which may interfere with the binding of SL to the receptor protein as a result. In addition, the results of crop safety assessment tests showed that D12 had no adverse effects on rice seed germination and seedling growth and development. The outcomes obtained from the present study suggested that D12 exhibited promise as a prospective antagonist of SL receptors, thereby displaying substantial efficacy in impeding the seed germination process of root parasitic weeds, providing a promising basis for rational design and development of further Striga-specific herbicides.

E4bp4-Cyp3a11 axis in high-fat diet-induced obese mice with weight fluctuation.

OBJECTIVE: Weight regain after weight loss is a challenge in obesity management. The metabolic changes and underlying mechanisms in obese people with weight fluctuation remain to be elucidated. In the present study, we aimed to profile the features and clinical significance of liver transcriptome in obese mice with weight regain after weight loss. METHODS: The male C57BL/6J mice were fed with standard chow diet or high-fat diet (HFD). After 9 weeks, the HFD-induced obese mice were randomly divided into weight gain (WG), weight loss (WL) and weight regain (WR) group. After 10 weeks of dietary intervention, body weight, fasting blood glucose (FBG), intraperitoneal glucose tolerance, triglycerides (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C) were measured. Morphological structure and lipid droplet accumulation in the liver were observed by H&E staining and oil red O staining, respectively. The liver transcriptome was detected by RNA sequencing. Protein expressions of liver cytochrome P450 3a11 (Cyp3a11) and E4 promoter-binding protein 4 (E4bp4) were determined by Western blot. RESULTS: After 10 weeks of dietary intervention, the body weight, FBG, glucose area under the curve, T-CHO and LDL-C in WL group were significantly lower than those in WG group (P < 0.05). At 4 weeks of HFD re-feeding, the mice in WR group presented body weight and T-CHO significantly lower than those in WG group, whereas higher than those in WL group (P < 0.05). Hepatic vacuolar degeneration and lipid droplet accumulation in the liver were significantly alleviated in WL group and WR group, compared to those in WG group. The liver transcriptome associated with lipid metabolism was significantly altered during weight fluctuation in obese mice. Compared with those in WG group, Cyp3a11 in the liver was significantly upregulated, and E4bp4 was significantly downregulated in WL and WR groups. CONCLUSION: Obese mice experience weight regain after weight loss by HFD re-feeding, but their glucose and lipid metabolism disorders are milder than those induced by the persistence of obesity. Downregulated E4bp4 and upregulated Cyp3a11 are detected in obese mice after weight loss, suggesting that the E4bp4-Cyp3a11 axis may involved in metabolic mechanisms underlying weight regulation.

Ketogenic diet alleviates ß-cell dedifferentiation but aggravates hepatic lipid accumulation in db/db mice.

OBJECTIVE: The aim of this study was to explore the effect of the ketogenic diet (KD) on ß-cell dedifferentiation and hepatic lipid accumulation in db/db mice. METHODS: After a 3-wk habituation, male db/db mice ages 8 wk were assigned into one of three groups: normal diet (ND), KD, and 75% calorie restriction (CR) group. Free access to a standard diet, a KD, and 75% of a standard diet, respectively, were given to each group. Additionally, sex-matched 8-wk-old C57BL/6 mice were used to construct a control (C) group. After a 4-wk dietary intervention, mouse body weight, fasting blood glucose (FBG), blood lipids, fasting insulin (FINS), glucose tolerance, and ß-hydroxybutyric acid level were measured. The morphologies of the islet and liver were observed by hematoxylin and eosin staining. Positive expressions of ß-cell-specific transcription factors in mouse islets were determined by double immunofluorescence staining. The size and number of lipid droplets in mouse liver were examined by Oil Red O staining. Real-time quantitative reverse transcription polymerase chain reaction detected relative levels of adipogenesis-associated and lipolysis-associated genes in mouse liver. Additionally, expressions of CD36 protein in the mouse liver were determined by immunohistochemical staining and Western blot. RESULTS: After a 4-wk dietary intervention, FBG, FINS, and glucose area under the curve in the KD group became significantly lower than in the ND group (all P < 0.05). Regular morphology of mouse islets was observed in the KD group, with an increased number of islet cells. The KD significantly reversed the decrease in ß-cell number, disarrangement of ß-cells, decline of ß/α-cell ratio, and downregulation of ß-cell-specific transcription factors in db/db mice. Serum levels of triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol were comparable between the ND and KD groups. In contrast, serum triacylglycerol levels were significantly lower in the CR group than in the ND group (P < 0.05). Vacuolar degeneration and lipid accumulation in the liver were more prominent in the KD group than in the ND and CR groups. The mRNA levels of Pparα and Acox1 in the KD group were lower than those in the ND group, although no significant differences were detected. Relative levels of Cd36 and inflammatory genes in the mouse liver were significantly higher in the KD group than in the ND group (all P < 0.05). CONCLUSION: The KD significantly reduced FBG and FINS and improved glucose tolerance in db/db mice by upregulating ß-cell-specific transcription factors and reversing ß-cell dedifferentiation. However, the KD also induced hepatic lipid accumulation and aggravated inflammatory response in the liver of db/db mice.

Mechanism of Prunella vulgaris L. and luteolin in restoring Tfh/Tfr balance and alleviating oxidative stress in Graves' disease.

BACKGROUND: The pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. PURPOSE: This study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). METHODS: High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. RESULTS: A total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. CONCLUSION: XKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS.

Development of matrix certified reference material for accurate determination of docosahexaenoic acid in milk powder.

A novel matrix certified reference material (CRM) of docosahexaenoic acid in milk powder [GBW (E) 100641] was first developed. The CRM candidates was prepared by adding appropriate levels of docosahexaenoic acid to cow's milk, then powder sprayed, lyophilized, mixed, dispensed and sterilized. An optimized acetylchloride-methanol method was proposed and used for the characterization. The CRM characterization was carried out in six laboratories in accordance with ISO Guide 35 requirements. The certified value of CRM was 0.69 mg/g with an uncertainty of 0.08 mg/g (k = 2). The CRM was sufficiently homogeneous between and within bottles and stable up to 6 month at -20℃ and 7 days below 50 â„ƒ. The uncertainty was evaluated by combing the contributions from characterization, homogeneity and stability. Thus, the CRM can be used for quality control and method validation to ensure the accurate and reliable measurements of docosahexaenoic acid in milk for quality monitoring.

Xiehuo Xiaoying decoction inhibits Tfh cell expansion and promotes Tfr cell amplification to ameliorate Graves' disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiehuo Xiaoying decoction (XHXY) has shown great potential in the treatment of GD, but its mechanism remains obscure. Increase of follicular helper T (Tfh) cells and reduction of follicular regulatory T (Tfr) cells contribute to a high thyrotropin receptor antibodies (TRAb) level and possible Graves' disease (GD). Oxidative stress (OS) disrupts T helper cell differentiation and aggravates autoimmunity. AIM OF THE STUDY: This study aimed to investigate whether XHXY decoction can ameliorate autoimmunity in GD via inhibiting OS and regulating Tfh and Tfr cells. MATERIALS AND METHODS: The main XHXY bioactive compounds were identified using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. GD was induced in the mice through three intramuscular injections of adenovirus expressing the TSH receptor. Then, the mice received oral gavage of XHXY (17 g/kg·d) and 34 g/kg·d) for 4 weeks. OS indicators were assessed. Flow cytometry was used to confirm the proportion of Tfh and Tfr cells in the lymph nodes and spleens of the mice. Cytokine expression levels were determined using enzyme-linked immunosorbent assay. Factors including interleukin-21, B-cell lymphoma-6, and forkhead box P3 (Foxp3) were detected using quantitative polymerase chain reaction. The mRNA and protein expression levels of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid-2-related factor 2 (Nrf2), and haem oxygenase 1 (HO-1) were detected using quantitative polymerase chain reaction and Western blotting, respectively. RESULTS: Twelve main ingredients of XHXY were identified. XHXY relieved GD by lowering thyroxine (p < 0.01) and TRAb levels (p < 0.01). XHXY ameliorated OS by decreasing the levels of NADPH oxidase 2 (p < 0.05), 4-hydroxynonenal (p < 0.01), and 8-oxo-2'-deoxyguanosine (p < 0.001). It inhibited Tfh cell expansion (p < 0.05), as well as the production of cytokine interleukin -21 (p < 0.01), interleukin -4 (p < 0.01) and transcription factor B-cell lymphoma 6 (p < 0.05). XHXY also induced Tfr cell amplification (p < 0.05), increased the production of interleukin -10 (p < 0.05) and transforming growth factor ß (p < 0.05) and the mRNA levels of Foxp3 (p < 0.05). Finally, the Tfh/Tfr ratio returned to normal. In addition, XHXY activated Nrf2 and HO-1 expression, but inhibited Keap1 activation. CONCLUSIONS: XHXY relieves autoimmunity in GD via inhibiting Tfh cell amplification and Tfr cell reduction, a mechanism which probably involves the Keap1/Nrf2 signaling pathway.

ERα positively regulated DNMT1 expression by binding to the gene promoter region in human breast cancer MCF-7 cells.

Estrogen receptors (ER) are expressed in approximately 65% of human breast cancer. Clinical trials and retrospective analyses showed that ER-positive (ER+) tumors were more vulnerable to development of chemotherapy resistance than ER-negative (ER-) tumors. The underlying mechanism is still to be elucidated. Aberrant DNA methylation has been recognized to be associated with cancer chemotherapy resistance. Recently, steroid hormone and their receptors have been found to be involved in the regulation of methyltransferases (DNMTs) and thereby contribute to chemotherapy resistance. The purpose of this study is to explore whether ERα could directly regulate the DNMTs expression. We first analyzed the methylation alterations and its correlation with the expression levels of three types of DNMTs in our established paclitaxel-resistant breast cancer lines, MCF-7(ER+)/PTX and MDA-MB-231(ER-)/PTX cell lines, using qMSP, real-time PCR and Western blot. Then we determined the function of ERα in regulation of DNMT1 using luciferase report gene systems. Our data demonstrated for the first time that ERα could upregulate DNMT1 expression by directly binding to the DNMT1 promoter region in MFC-7(ER+)/PTX cells.

Optimal design of model predictive controller based on transient search optimization applied to robotic manipulators.

Due to nonlinearity and uncertainty of the robotic manipulator, the design of the robot controller has a crucial impact on its performance of motion and trajectory tracking. In this paper, the linear parameter varying (LPV) - model predictive controller (MPC) of a two-link robot manipulator is established and then the controller's optimal parameters are determined via a newly developed meta-heuristic algorithm, transient search optimization (TSO). The proposed control method is verified by set point and nonlinear trajectory tracking. In the test of set-point tracking, the LPV-MPC scheme optimized by TSO has better performance compared to the computed torque controller (CTC) schemes tuned by TSO or other metaheuristic algorithms. In addition, good performances can also be observed in the tests of nonlinear trajectory tracking via the LPV-MPC scheme by TSO. Moreover, the robustness of the method to structural uncertainty is verified by setting a large system parameter deviation. Results reveal that we achieved some improvements in the optimization of MPC of the robot manipulator by employing the proposed method.