Development of diagnostic tools for detecting expression of resistance-associated esterases in the tobacco budworm, Heliothis virescens (F.)

Esterase-based metabolic resistance was studied using biochemical and biological assays with organophosphate (OP)- and pyrethroid (PYR)- resistant tobacco budworms, Heliothis virescens. In biochemical assays, results suggest that: (1) esterase activities toward all substrates used were enhanced in both resistant strains compared with the susceptible strain, suggesting that esterases were involved in resistance; (2) esterase profiles differed depending on the strain and substrate used, and these differences were visualized by using native polyacrylamide gel electrophoresis; 3) esterase activities toward some pyrethroid substrates were significantly higher (P ≤ 0.01) in the PYR-R strain than those in the OP-R strain. These results suggest that pyrethroid substrates may be useful indicators for detecting esterases associated with pyrethroid resistance. Finally, biochemical assays were modified for use on solid materials, and esterase substrates were tested in filter paper assays. Whereas some differences in color intensity were detected between susceptible and resistant strains, these differences were not dramatic. Thus, utility of these substrates in such assays appears limited at this time, but further research is warranted. In biological assays, two approaches were taken to improve the precision with which esterases associated with pyrethroid resistance were detected. First, bioassays were used to test effects of pyrethroid substrates and traditional synergists (e.g., piperonyl butoxide) on insecticide toxicity. Non-toxic pyrethroid esters enhanced pyrethroid toxicity to a greater extent than DEF, a compound widely used as an esterase inhibitor. In addition, synergism of profenofos and cypermethrin toxicity in both resistant strains by an oxidase inhibitor, 1, 2, 4-trichloro-3 (2-propynyloxy) benzene, suggests that P450 monooxygenases were also involved in resistance. The second method tested was to utilize bioactivated insecticides to detect esterases. Absence of negative cross-resistance to insecticides (i.e., acephate and indoxacarb) that are activated by esterases suggests that detoxication of these compounds in resistant insects proceeds more rapidly than their activation by esterases. Finally, levels of cross-resistance to tefluthrin and trans-fenfluthrin were lower than to permethrin and cypermethrin in both resistant strains, suggesting that resistance to insecticides in which sites for detoxifying enzymes (e.g., oxidases) are blocked develops more slowly than resistance to those in which metabolic sites are present

Exploration of Implementation of the Last Planner System of Production Control by Chinese Contractors: A Case Study

During the past two decades, Lean Construction has been utilized in over 200 pilot projects in different countries all over the world except for China. Although qualitative inquiries have been made regarding the applicability of the Last Planner System of Production Control (hereafter referred to as LPS) in China, on site exploration effort of LPS implementation in China is still lacking, and subsequently the clear strategies for implementation on site. The thesis presented the first on site exploration of LPS in China to the scholars and researchers from the lean community worldwide. The main method used in this thesis is case study and literature review. Case study was used to expose the challenges for implementing LPS in China while the literature review was used to find solutions for one challenge revealed in the case study. Major findings of this study include: (1) the main constraints of LPS in China are exclusion of foremen during the planning process, no update on planning information, and lack of cooperation among different parties; (2) the power distance inside the general contractor is relatively easy to solve comparing to the power distance between general contractors and subcontractors; (3) the team leader of the trade foremen can serve as the last planner in China. Findings from a literature review suggest that power distance can be reduced if top management authorizes changes to encourage and reward subordinates to express their opinions. This thesis recommends further research on the adaption of LPS in China. Future work on more pilot projects in China is needed to initiate the use of LPS by Chinese contractors, and then further increase the use of LPS worldwide

Stereoselective Hydrolysis of Pyrethroid-like Fluorescent Substrates by Human and Other Mammalian Liver Carboxylesterases

Mammalian hepatic carboxylesterases (CEs) play important roles in the detoxification of ester-containing pyrethroids, which are widely used for the control of agricultural pests and disease vectors such as mosquitoes. Pyrethroids and pyrethroid-like fluorescent substrates exhibit a consistent pattern of stereoselective hydrolysis by a recombinant murine hepatic CE. We sought to understand whether this pattern is maintained in other hepatic CEs and to unravel the origin of the stereoselectivity. We found that all hepatic CEs tested displayed a consistent pattern of stereoselective hydrolysis: the chiral center(s) in the acid moiety more strongly influenced stereoselective hydrolysis than the chiral center in the alcohol moiety. For cypermethrin analogues with a cyclopropane ring in the acid moiety, trans-isomers were generally hydrolyzed faster than the corresponding cis-isomers. For fenvalerate analogues without a cyclopropane ring in the acid moiety, 2R-isomers were better substrates than 2S-isomers. These general hydrolytic patterns were examined by modeling the pyrethroid-like analogues within the active site of the crystal structure of human carboxylesterase 1 (hCE1). Stereoselective steric clashes were found to occur between the acid moieties and either the catalytic Ser loop (residues 219-225) or the oxyanion hole (residues140-144). These clashes appeared to explain the stereopreference between trans- and cis-isomers of cypermethrin analogues, and the 2R- and 2S-isomers of fenvalerate analogues by hCE1. The implications these findings have on the design and use of effective pesticides are discussed

Downregulation of Long Non-coding RNA FALEC Inhibits Gastric Cancer Cell Migration and Invasion Through Impairing ECM1 Expression by Exerting Its Enhancer-Like Function

Long non-coding RNAs (lncRNAs) have been shown to play important roles in many human diseases. However, their functions and mechanisms in tumorigenesis and development remain largely unknown. Here, we demonstrated that focally amplified lncRNA in epithelial cancer (FALEC) was upregulated and significantly correlated with lymph node metastasis, TNM stage in gastric cancer (GC). Further experiments revealed that FALEC knockdown significantly inhibited GC cells migration and invasion in vitro. Mechanistic investigations demonstrated that small interfering RNA-induced silencing of FALEC decreased expression of the nearby gene extracellular matrix protein 1 (ECM1) in cis. Additionally, ECM1 and FALEC expression were positively correlated, and high levels of ECM1 predicted shorter survival time in GC patients. Our results suggest that the downregulation of FALEC significantly inhibited the migration and invasion of GC cells through impairing ECM1 expression by exerting an enhancer-like function. Our work provides valuable information and a novel promising target for developing new therapeutic strategies in GC

Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos

Abstract Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental exposure to these pesticides. In this study, carboxylesterase and AChE activity, cytochrome P4501A (CYP1A) protein levels, and mortality were measured in individual juvenile Chinook salmon (Oncorhynchus tshawytscha) following exposure to an OP (chlorpyrifos) and a pyrethroid (esfenvalerate). As expected, high doses of chlorpyrifos and esfenvalerate were acutely toxic, with nominal concentrations (100 and 1 g/l, respectively) causing 100% mortality within 96 h. Exposure to chlorpyrifos at a high dose (7.3 g/l), but not a low dose (1.2 g/l), significantly inhibited AChE activity in both brain and muscle tissue (85% and 92% inhibition, respectively), while esfenvalerate exposure had no effect. In contrast, liver carboxylesterase activity was significantly inhibited at both the low and high chlorpyrifos dose exposure (56% and 79% inhibition, respectively), while esfenvalerate exposure still had little effect. The inhibition of carboxylesterase activity at levels of chlorpyrifos that did not affect AChE activity suggests that some salmon carboxylesterase isozymes may be more sensitive than AChE to inhibition by OPs. CYP1A protein levels were ∼30% suppressed by chlorpyrifos exposure at the high dose, but esfenvalerate had no effect. Three teleost species, Chinook salmon, medaka (Oryzias latipes) and Sacramento splittail (Pogonichthys macrolepidotus), were examined for their ability to hydrolyze a series of pyrethroid surrogate substrates and in all cases hydrolysis activity was undetectable. * Corresponding author. Wheelock et al. / Aquatic Toxicology 74 (2005) 172-192 173 Together these data suggest that (1) carboxylesterase activity inhibition may be a more sensitive biomarker for OP exposure than AChE activity, (2) neither AChE nor carboxylesterase activity are biomarkers for pyrethroid exposure, (3) CYP1A protein is not a sensitive marker for these agrochemicals and (4) slow hydrolysis rates may be partly responsible for acute pyrethroid toxicity in fish

Examination and Modification of Multi-Factor Model in Explaining Stock Excess Return with Hybrid Approach in Empirical Study of Chinese Stock Market

To search significant variables which can illustrate the abnormal return of stock price, this research is generally based on the Fama-French five-factor model to develop a multi-factor model. We evaluated the existing factors in the empirical study of Chinese stock market and examined for new factors to extend the model by OLS and ridge regression model. With data from 2007 to 2018, the regression analysis was conducted on 1097 stocks separately in the market with computer simulation based on Python. Moreover, we conducted research on factor cyclical pattern via chi-square test and developed a corresponding trading strategy with trend analysis. For the results, we found that except market risk premium, each industry corresponds differently to the rest of six risk factors. The factor cyclical pattern can be used to predict the direction of seven risk factors and a simple moving average approach based on the relationships between risk factors and each industry was conducted in back-test which suggested that SMB (size premium), CMA (investment growth premium), CRMHL (momentum premium), and AMLH (asset turnover premium) can gain positive return

Soyasaponin Ag inhibits triple-negative breast cancer progression via targeting the DUSP6/MAPK signaling

Introduction. Soyasaponins are triterpenoid glycosides discovered in soybean and have anti-cancer properties. Soyasaponin A was reported to repress estrogen-insensitive breast cancer cell proliferation. This study intends to explore the role of one isomer of soyasaponin A, i.e. soyasaponin Ag (Ssa Ag), in triple-negative breast cancer (TNBC) development. Material and methods. Bioinformatic databases were used to predict DUSP6 expression in breast cancer (BC) as well as the correlation between the expression of DUSP6 (or MAPK1, MAPK14) with the prognosis of patients with BC. The expression of DUSP6/MAPK signaling-related genes (DUSP6, MAPK1, and MAPK14) in TNBC cell lines was assessed via Western blot analysis and RT-qPCR. Levels of cell apoptosis proteins (Bax and Bcl-2) in TNBC cells were assessed via Western blot analysis. CCK-8 assay, colony formation assay, and flow cytometry analysis were conducted for the measurement of TNBC cell growth and apoptosis. In vivo xenograft assay was employed for investigating the biological influence of Ssa Ag on tumor growth. Results. The poor prognosis of BC patients was linked to the aberrant expression of DUSP6/MAPK pathwaygenes. Low expression of DUSP6 or high expression of MAPK1 (or MAPK14) was correlated to poor prognosis. DUSP6 was downregulated while MAPK1 and MAPK14 were upregulated in TNBC cells versus normal cells. Ssa Ag upregulated DUSP6 expression while downregulated MAPK1 and MAPK14 expression, inhibiting the MAPK signaling pathway. Additionally, Ssa Ag promoted in vitro TNBC cell apoptosis and restrained cell growth, and repressed in vivo tumor growth. Conclusions. Ssa Ag inhibited TNBC progression via upregulating DUSP6 and inactivating the MAPK signaling pathway

Clinical utilization of methylprednisolone in conjunction with tranexamic acid for accelerated rehabilitation in total hip arthroplasty

Abstract Purpose This study aimed to evaluate the efficacy and safety of combined methylprednisolone (MP) and tranexamic acid (TXA) in promoting accelerated rehabilitation following total hip arthroplasty (THA). We further investigated effective strategies for rapid rehabilitation post-THA. Methods Conducted as a randomized controlled trial involving 80 patients, the study allocated subjects into two groups. The control group received saline and TXA, whereas the experimental group was administered with an additional dose of MP. Several clinical parameters, including markers of inflammation, pain, nausea, and coagulation factors, were meticulously assessed in both groups. Results It was observed that the group receiving the MP + TXA treatment showcased significant reductions in postoperative levels of CRP and IL-6, as well as an alleviation in pain scores. Furthermore, this group demonstrated lower incidences of postoperative nausea and fatigue, facilitating enhanced hip joint mobility. Interestingly, this group did exhibit blood glucose fluctuations within the first 24 h postoperatively. However, there was no notable difference between the groups concerning transfusion rate, postoperative hospital stay duration, and coagulation profile, and no severe complications were reported. Conclusion The findings suggest that the combined administration of MP and TXA can appreciably enhance postoperative recovery, by reducing inflammatory markers, alleviating pain, reducing nausea and fatigue, and improving hip mobility, without leading to an increased risk of severe perioperative complications. This highlights the potential role of this combined therapy in facilitating improved postoperative patient experiences