Evaluating the impact of test-trace-isolate for COVID-19 management and alternative strategies.

There are many contrasting results concerning the effectiveness of Test-Trace-Isolate (TTI) strategies in mitigating SARS-CoV-2 spread. To shed light on this debate, we developed a novel static-temporal multiplex network characterizing both the regular (static) and random (temporal) contact patterns of individuals and a SARS-CoV-2 transmission model calibrated with historical COVID-19 epidemiological data. We estimated that the TTI strategy alone could not control the disease spread: assuming R0 = 2.5, the infection attack rate would be reduced by 24.5%. Increased test capacity and improved contact trace efficiency only slightly improved the effectiveness of the TTI. We thus investigated the effectiveness of the TTI strategy when coupled with reactive social distancing policies. Limiting contacts on the temporal contact layer would be insufficient to control an epidemic and contacts on both layers would need to be limited simultaneously. For example, the infection attack rate would be reduced by 68.1% when the reactive distancing policy disconnects 30% and 50% of contacts on static and temporal layers, respectively. Our findings highlight that, to reduce the overall transmission, it is important to limit contacts regardless of their types in addition to identifying infected individuals through contact tracing, given the substantial proportion of asymptomatic and pre-symptomatic SARS-CoV-2 transmission.

Photogenerated chlorine radicals activate C(sp3)-H bonds of alkylbenzenes to access quinazolinones.

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

UPLC-Q-TOF-MS/MS-Based Targeted Discovery of Chetomin Analogues from Chaetomium cochliodes.

Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.

Pattern dynamics of networked epidemic model with higher-order infections.

Current research on pattern formations in networked reaction-diffusion (RD) systems predominantly focuses on the impacts of diffusion heterogeneity between nodes, often overlooking the contact heterogeneity between individuals within nodes in the reaction terms. In this paper, we establish a networked RD model incorporating infection through higher-order interaction in simplicial complexes in the reaction terms. Through theoretical and numerical analysis, we find that these higher-order interactions may induce Turing instability in the system. Notably, the relationship between the size of the Turing instability range and the average 2-simplices degree within nodes can be approximated by a quadratic function. Additionally, as the average 2-simplices degree increases, the amplitude of the patterns exhibits three distinct trends: increasing, decreasing, and initially increasing then decreasing, while the average infection density increases consistently. We then provide a possible explanation for these observations. Our findings offer new insights into the effects of contact heterogeneity within nodes on networked pattern formations, thereby informing the development of epidemic prevention and control measures.

Vegetation restoration strategies in arid or semi-arid regions-From the perspective of optimal control.

Inappropriate human activities contribute to the degradation of ecosystems in arid or semi-arid regions. Therefore, emphasizing the importance of strategies for restoring vegetation in these areas cannot be overstated. However, there has been insufficient research on how to develop effective restoration strategies at minimal cost. This paper addresses this gap by studying how optimizing the spatiotemporal distribution of human activities through local and boundary controls can reduce the level of desertification in vegetation pattern structures, thereby facilitating the recovery of arid land vegetation. The results indicate that vegetation restoration depends on the proportion and number of human activity areas, with a trade-off between them. Furthermore, consistent conclusions were obtained on circular regions, demonstrating the robustness of the approach to boundary shapes. This paper aims to offer new insights into the restoration of arid land vegetation and the prevention of catastrophic ecosystem changes from the perspective of optimal control.

Structure, physicochemical properties, and biological activities of protein hydrolysates from Zanthoxylum seed.

BACKGROUND: Zanthoxylum seed, as a low-cost and easily accessible plant protein resource, has good potential in the food industry. But protein and its hydrolysates from Zanthoxylum seed are underutilized due to the dearth of studies on them. This study aimed to investigate the structure and physicochemical and biological activities of Zanthoxylum seed protein (ZSP) hydrolysates prepared using Protamex®, Alcalase®, Neutrase®, trypsin, or pepsin. RESULTS: Hydrolysis using each of the five enzymes diminished average particle size and molecular weight of ZSP but increased random coil content. ZSP hydrolysate prepared using pepsin had the highest degree of hydrolysis (24.07%) and the smallest molecular weight (<13 kDa) and average particle size (129.80 nm) with the highest solubility (98.9%). In contrast, ZSP hydrolysate prepared using Alcalase had the highest surface hydrophobicity and foaming capacity (88.89%), as well as the lowest foam stability (45.00%). Moreover, ZSP hydrolysate prepared using Alcalase exhibited the best hydroxyl-radical scavenging (half maximal inhibitory concentration (IC50 ) 1.94 mg mL-1 ) and ferrous-ion chelating (IC50 0.61 mg mL-1 ) activities. Additionally, ZSP hydrolysate prepared using pepsin displayed the highest angiotensin-converting enzyme inhibition activity (IC50 0.54 mg mL-1 ). CONCLUSION: These data showed that enzyme hydrolysis improved the physicochemical properties of ZSP, and enzymatic hydrolysates of ZSP exhibited significant biological activity. These results provided validation for application of ZSP enzymatic hydrolysates as antioxidants and antihypertensive agents in the food or medicinal industries. © 2023 Society of Chemical Industry.

Structure, functional and physicochemical properties of lotus seed protein under different pH environments.

BACKGROUND: The present study investigated the structure, functional and physicochemical properties of lotus seed protein (LSP) under different pH environments. The structures of LSP were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy (FTIR), zeta potential, particle size distributions, free sulfhydryl and rheological properties. The functional and physicochemical properties of LSP were characterized by color, foaming property, emulsification property, solubility, oil holding capacity, water holding capacity, differential scanning calorimetry analysis and surface hydrophobicity. RESULTS: LSP was mainly composed of eight subunits (18, 25, 31, 47, 51, 56, 65 and 151 kDa), in which the richest band was 25 kDa. FTIR results showed that LSP had high total contents of α-helix and ß-sheet (44.81-46.85%) in acidic environments. Meanwhile, there was more ß-structure and random structure in neutral and alkaline environments (pH 7.0 and 9.0). At pH 5.0, LSP had large particle size (1576.98 nm), high emulsion stability index (91.43 min), foaming stability (75.69%) and water holding capacity (2.21 g g-1), but low solubility (35.98%), free sulfhydryl content (1.95 µmol g-1) and surface hydrophobicity (780). DSC analysis showed the denaturation temperatures (82.23 °C) of LSP at pH 5.0 was higher than those (80.10, 80.52 and 71.82 °C) at pH 3.0, 7.0 and 9.0. The analysis of rheological properties showed that LSP gel had high stability and great strength in an alkaline environment. CONCLUSION: The findings of the present study are anticipated to serve as a valuable reference for the implementation of LSP in the food industry. © 2024 Society of Chemical Industry.

The structural characteristics and physicochemical properties of mung bean protein hydrolysate of protamex induced by ultrasound.

BACKGROUND: The limited physicochemical properties (such as low foaming and emulsifying capacity) of mung bean protein hydrolysate restrict its application in the food industry. Ultrasound treatment could change the structures of protein hydrolysate to accordingly affect its physicochemical properties. The aim of this study was to investigate the effects of ultrasound treatment on the structural and physicochemical properties of mung bean protein hydrolysate of protamex (MBHP). The structural characteristics of MBHP were evaluated using tricine sodium dodecylsulfate-polyacrylamide gel electrophoresis, laser scattering, fluorescence spectrometry, etc. Solubility, fat absorption capacity and foaming, emulsifying and thermal properties were determined to characterize the physicochemical properties of MBHP. RESULTS: MBHP and ultrasonicated-MBHPs (UT-MBHPs) all contained five main bands of 25.8, 12.1, 5.6, 4.8 and 3.9 kDa, illustrating that ultrasound did not change the subunits of MBHP. Ultrasound treatment increased the contents of α-helix, ß-sheet and random coil and enhanced the intrinsic fluorescence intensity of MBHP, but decreased the content of ß-turn, which demonstrated that ultrasound modified the secondary and tertiary structures of MBHP. UT-MBHPs exhibited higher solubility, foaming capacity and emulsifying properties than MBHP, among which MBHP-330 W had the highest solubility (97.32%), foaming capacity (200%), emulsification activity index (306.96 m2 g-1 ) and emulsion stability index (94.80%) at pH 9.0. CONCLUSION: Ultrasound treatment enhanced the physicochemical properties of MBHP, which could broaden its application as a vital ingredient in the food industry. © 2023 Society of Chemical Industry.

A hierarchical intervention scheme based on epidemic severity in a community network.

As there are no targeted medicines or vaccines for newly emerging infectious diseases, isolation among communities (villages, cities, or countries) is one of the most effective intervention measures. As such, the number of intercommunity edges ([Formula: see text]) becomes one of the most important factor in isolating a place since it is closely related to normal life. Unfortunately, how [Formula: see text] affects epidemic spread is still poorly understood. In this paper, we quantitatively analyzed the impact of [Formula: see text] on infectious disease transmission by establishing a four-dimensional [Formula: see text] edge-based compartmental model with two communities. The basic reproduction number [Formula: see text] is explicitly obtained subject to [Formula: see text] [Formula: see text]. Furthermore, according to [Formula: see text] with zero [Formula: see text], epidemics spread could be classified into two cases. When [Formula: see text] for the case 2, epidemics occur with at least one of the reproduction numbers within communities greater than one, and otherwise when [Formula: see text] for case 1, both reproduction numbers within communities are less than one. Remarkably, in case 1, whether epidemics break out strongly depends on intercommunity edges. Then, the outbreak threshold in regard to [Formula: see text] is also explicitly obtained, below which epidemics vanish, and otherwise break out. The above two cases form a severity-based hierarchical intervention scheme for epidemics. It is then applied to the SARS outbreak in Singapore, verifying the validity of our scheme. In addition, the final size of the system is gained by demonstrating the existence of positive equilibrium in a four-dimensional coupled system. Theoretical results are also validated through numerical simulation in networks with the Poisson and Power law distributions, respectively. Our results provide a new insight into controlling epidemics.

Changes in quality components and antioxidant activity of peony seed soy sauce during low-salt solid-state fermentation.

BACKGROUND: In this study, the fermentation conditions of peony seed soy sauce (PSSS) koji were optimized by response surface method, and the quality components and antioxidant activity of PSSS were investigated at different low-salt solid-state fermentation stages. RESULTS: Results of response surface method showed that the optimal fermentation conditions were 460.6 g kg-1 water content, 48.6 h culture time, 31.5 °C culture temperature and ratio 2.1:1 (w/w) of peony seed meal:wheat bran, with the highest neutral protease activity (2193.78 U g-1 ) of PSSS koji. PSSS had the highest amino acid nitrogen (7.69 g L-1 ), salt-free soluble solids (185.26 g L-1 ), total free amino acids (49.03 g L-1 ), essential free amino acids (19.58 g L-1 ) and umami free amino acids (16.64 g L-1 ) at 20 days of fermentation. The highest total phenolics were 5.414 g gallic acid equivalent L-1 and total flavonoids 0.617 g rutin equivalent L-1 , as well as the highest DPPH radical scavenging activity (86.19%) and reducing power (0.8802, A700 ) of PSSS fermented at 30 days. Sensory evaluation showed that fermentation of 20 days and 25 days could produce a better taste and aroma of PSSS than 15 days and 30 days. CONCLUSION: PSSS had the highest quality components in the middle of fermentation (20 days) and the highest antioxidant activity in the late fermentation period (30 days). These results demonstrated that peony seed meal could be used to produce high-quality soy sauce with high antioxidant activity. © 2023 Society of Chemical Industry.

[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis.

Studies have shown that diabetes is associated with the occurrence of neurodegenerative diseases and cognitive decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The superior efficacy of liraglutide (LIRA) for cognitive impairment and numerous neurodegenerative diseases has been widely demonstrated. This study determined the effects of LIRA on diabetic cognitive impairment and on the levels of oxidative stress, lipid peroxidation, iron metabolism and ferroptosis in the hippocampus. Mice were injected daily with liraglutide (200 µg/kg/d) for 5 weeks. LIRA could repair damaged neurons and synapses, and it increased the protein expression levels of PSD 95, SYN, and BDNF. Furthermore, LIRA significantly decreased oxidative stress and lipid peroxidation levels by downregulating the production of ROS and MDA and upregulating SOD and GSH-Px in the serum and hippocampus, and the upregulation of SOD2 expression was also proven. The decreased levels of TfR1 and the upregulation of FPN1 and FTH proteins observed in the LIRA-treated db/db group were shown to reduce iron overload in the hippocampus, whereas the increased expression of Mtft and decreased expression of Mfrn in the mitochondria indicated that mitochondrial iron overload was ameliorated. Finally, LIRA was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4; simultaneously, the damage to the mitochondria observed by TEM was also repaired. For the first time, we proved in the T2DM model that ferroptosis occurs in the hippocampus, which may play a role in diabetic cognitive impairment. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetic cognitive disorders and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.

What is the role of aerosol transmission in SARS-Cov-2 Omicron spread in Shanghai?

The Omicron transmission has infected nearly 600,000 people in Shanghai from March 26 to May 31, 2022. Combined with different control measures taken by the government in different periods, a dynamic model was constructed to investigate the impact of medical resources, shelter hospitals and aerosol transmission generated by clustered nucleic acid testing on the spread of Omicron. The parameters of the model were estimated by least square method and MCMC method, and the accuracy of the model was verified by the cumulative number of asymptomatic infected persons and confirmed cases in Shanghai from March 26 to May 31, 2022. The result of numerical simulation demonstrated that the aerosol transmission figured prominently in the transmission of Omicron in Shanghai from March 28 to April 30. Without aerosol transmission, the number of asymptomatic subjects and symptomatic cases would be reduced to 130,000 and 11,730 by May 31, respectively. Without the expansion of shelter hospitals in the second phase, the final size of asymptomatic subjects and symptomatic cases might reach 23.2 million and 4.88 million by May 31, respectively. Our results also revealed that expanded vaccination played a vital role in controlling the spread of Omicron. However, even if the vaccination rate were 100%, the transmission of Omicron should not be completely blocked. Therefore, other control measures should be taken to curb the spread of Omicron, such as widespread antiviral therapies, enhanced testing and strict tracking quarantine measures. This perspective could be utilized as a reference for the transmission and prevention of Omicron in other large cities with a population of 10 million like Shanghai.

Spatial dynamics of a vegetation model with uptake-diffusion feedback in an arid environment.

Vegetation patterns with a variety of structures is amazing phenomena in arid or semi-arid areas, which can identify the evolution law of vegetation and are typical signals of ecosystem functions. Many achievements have been made in this respect, yet the mechanisms of uptake-diffusion feedback on the pattern structures of vegetation is not fully understood. To well reveal the influences of parameters perturbation on the pattern formation of vegetation, we give a comprehensive analysis on a vegetation-water model in the forms of reaction-diffusion equation which is posed by Zelnik et al. (Proc Natl Acad Sci 112:12,327-12,331, 2015). We obtain the exact parameters range for stationary patterns and show the dynamical behaviors near the bifurcation point based on nonlinear analysis. It is found that the model has the properties of spot, labyrinth and gap patterns. Moreover, water diffusion rate prohibits the growth of vegetation while shading parameter promotes the increase of vegetation biomass. Our results show that gradual transitions from uniform state to gap pattern can occur for suitable value of parameters which may induce the emergence of desertification.

Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) protects against focal cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

CONTEXT: Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) is a compound preparation commonly used for treating cerebral ischaemia/reperfusion injury in ischaemic stroke in China. However, its potential mechanisms on ischaemic stroke remain unknown. OBJECTIVE: This study explores the potential mechanisms of Xingxiong injection in vivo or in vitro. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly assigned to five groups: the sham (normal saline), the model (normal saline) and the Xingxiong injection groups (12.5, 25 or 50 mL/kg). The rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 14 d. Xingxiong injection was administered via intraperitoneal (i.p.) injection immediately after ischaemia induction for 14 d. Afterwards, rats were sacrificed at 14 d induced by administration of Xingxiong injection. RESULTS: Xingxiong injection significantly reduces infarct volume (23%) and neurological deficit scores (93%) compared with the MCAO/R group. Additionally, Xingxiong injection inhibits the loss in mitochondrial membrane potential (43%) and reduces caspase-3 level (44%), decreases NOX (41%), protein carbonyl (29%), 4-HNE (40%) and 8-OhdG (41%) levels, inhibits the expression of inflammatory factors, such as TNF-α (26%), IL-1ß (34%), IL-6 (39%), MCP-1 (36%), CD11a (41%) and ICAM-1 (43%). Moreover, Xingxiong injection can increase p-Akt/Akt (35%) and Nrf2 (47%) protein expression and inhibit NLRP3 (42%) protein expression. CONCLUSIONS: Xingxiong injection prevents cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome. These findings provide experimental evidence for clinical use of drugs in the treatment of ischaemic stroke.

[Research progress on pharmacology of butylphthalide and its derivatives].

The butylphthalide(NBP), a colorless or light yellow viscous oily component isolated from celery seeds, has the effects of anti-inflammation, anti-oxidative stress, protecting blood-brain barrier, improving cerebral microcirculation, and promoting angiogenesis. It can protect the neurological function of patients with ischemic stroke through a variety of mechanisms, improve the symptoms of patients, and contribute to the long-term recovery of them. Therefore, independently developed in China, NBP was approved by State Food and Drug Administration for the clinical treatment of stroke patients in 2002. At the same time, owing to the complex multi-target pharmacological mechanism, NBP has been frequently used in clinical practice. As frequently verified, it has obvious effects in the treatment of other neurological diseases such as Alzheimer's disease, vascular dementia, Parkinson's disease, autoimmune diseases, depression, traumatic central nervous system injury. Moreover, it demonstrates significant pharmacological effects on non-neurological diseases such as diabetes mellitus and myocardial infarction. Therefore, this study summarizes the research progress on roles of NBP in nervous system diseases and non-nervous system diseases, and the pharmacological characteristics and mechanisms of NBP, which is expected to lay a basis for research on related targets.

Sensitivity assessment and optimal economic evaluation of a new COVID-19 compartmental epidemic model with control interventions.

Optimal economic evaluation is pivotal in prioritising the implementation of non-pharmaceutical and pharmaceutical interventions in the control of diseases. Governments, decision-makers and policy-makers broadly need information about the effectiveness of a control intervention concerning its cost-benefit to evaluate whether a control intervention offers the best value for money. The outbreak of COVID-19 in December 2019, and the eventual spread to other parts of the world, have pushed governments and health authorities to take drastic socioeconomic, sociocultural and sociopolitical measures to curb the spread of the virus, SARS-CoV-2. To help policy-makers, health authorities and governments, we propose a Susceptible, Exposed, Asymptomatic, Quarantined asymptomatic, Severely infected, Hospitalized, Recovered, Recovered asymptomatic, Deceased, and Protective susceptible (individuals who observe health protocols) compartmental structure to describe the dynamics of COVID-19. We fit the model to real data from Ghana and Egypt to estimate model parameters using standard incidence rate. Projections for disease control and sensitivity analysis are presented using MATLAB. We noticed that multiple peaks (waves) of COVID-19 for Ghana and Egypt can be prevented if stringent health protocols are implemented for a long time and/or the reluctant behaviour on the use of protective equipment by individuals are minimized. The sensitivity analysis suggests that: the rate of diagnoses and testing, the rate of quarantine through doubling enhanced contact tracing, adhering to physical distancing, adhering to wearing of nose masks, sanitizing-washing hands, media education remains the most effective measures in reducing the control reproduction number R c , to less than unity in the absence of vaccines and therapeutic drugs in Ghana and Egypt. Optimal control and cost-effectiveness analysis are rigorously studied. The main finding is that having two controls (transmission reduction and case isolation) is better than having one control, but is economically expensive. In case only one control is affordable, then transmission reduction is better than case isolation. Hopefully, the results of this research should help policy-makers when dealing with multiple waves of COVID-19.

Feedforward Control of Plant Nitrate Transporter NRT1.1 Biphasic Adaptive Activity.

Defective nitrate signaling in plants causes disorder in nitrogen metabolism, and it negatively affects nitrate transport systems, which toggle between high- and low-affinity modes in variable soil nitrate conditions. Recent discovery of a plasma membrane nitrate transceptor protein NRT1.1-a transporter cum sensor-provides a clue on this toggling mechanism. However, the general mechanistic description still remains poorly understood. Here, we illustrate adaptive responses and regulation of NRT1.1-mediated nitrate signaling in a wide range of extracellular nitrate concentrations. The results show that the homodimeric structure of NRT1.1 and its dimeric switch play an important role in eliciting specific cytosolic calcium waves sensed by the calcineurin-B-like calcium sensor CBL9, which activates the kinase CIPK23, in low nitrate concentration that is, however, impeded in high nitrate concentration. Nitrate binding at the high-affinity unit initiates NRT1.1 dimer decoupling and priming of the Thr101 site for phosphorylation by CIPK23. This phosphorylation stabilizes the NRT1.1 monomeric state, acting as a high-affinity nitrate transceptor. However, nitrate binding in both monomers, retaining the unmodified NRT1.1 state through dimerization, attenuates CIPK23 activity and thereby maintains the low-affinity mode of nitrate signaling and transport. This phosphorylation-led modulation of NRT1.1 activity shows bistable behavior controlled by an incoherent feedforward loop, which integrates nitrate-induced positive and negative regulatory effects on CIPK23. These results, therefore, advance our molecular understanding of adaptation in fluctuating nutrient availability and are a way forward for improving plant nitrogen use efficiency.

Emodin Inhibits Resistance to Imatinib by Downregulation of Bcr-Abl and STAT5 and Allosteric Inhibition in Chronic Myeloid Leukemia Cells.

Imatinib-resistance is a significant concern for Bcr-Abl-positive chronic myelogenous leukemia (CML) treatment. Emodin, the predominant compound of traditional medicine rhubarb, was reported to inhibit the multidrug resistance by downregulating P-glycoprotein of K562/ADM cells with overexpression of P-glycoprotein in our previous studies. In the present study, we found that emodin can be a potential inhibitor for the imatinib-resistance in K562/G01 cells which are the imatinib-resistant subcellular line of human chronic myelogenous leukemia cells with overexpression of breakpoint cluster region-abelson (Bcr-Abl) oncoprotein. Emodin greatly enhanced cell sensitivity to imatinib, suppressed resistant cell proliferation and increased potentiated apoptosis induced by imatinib in K562/G01 cells. After treatment of emodin and imatinib together, the levels of p-Bcr-Abl and Bcr-Abl were significantly downregulated. Moreover, Bcr-Abl important downstream target, STAT5 and its phosphorylation were affected. Furthermore, the expression of Bcr-Abl and signal transducers and activators of transcription 5 (STAT5) related molecules, including c-MYC, MCL-1, poly(ADP-ribose)polymerase (PARP), Bcl-2 and caspase-3, were changed. Emodin also decreased Src expression and its phosphorylation. More importantly, emodin simultaneously targeted both the ATP-binding and allosteric sites on Bcr-Abl by molecular docking, with higher affinity with the myristoyl-binding site for enhanced Bcr-Abl kinase inhibition. Overall, these data indicated emodin might be an effective therapeutic agent for inhibiting resistance to imatinib in CML treatment.

Estrogen Abolishes the Repression Role of gga-miR-221-5p Targeting ELOVL6 and SQLE to Promote Lipid Synthesis in Chicken Liver.

Few studies have been conducted regarding the biological function and regulation role of gga-miR-221-5p in the liver. We compared the conservation of miR-221-5p among species and investigated the expression pattern of gga-miR-221-5p, validating the direct target genes of gga-miR-221-5p by dual luciferase reporter assay, the biological function of gga-miR-221-5p in the liver was studied by gga-miR-221-5p overexpression and inhibition. Furthermore, we explored the regulation of gga-miR-221-5p and its target genes by treatment with estrogen and estrogen antagonists in vivo and in vitro. The results showed that miR-221-5p was highly conserved among species, expressed in all tested tissues and significantly downregulated in peak-laying hen liver compared to pre-laying hen liver. Gga-miR-221-5p could directly target the expression of elongase of very long chain fatty acids 6 (ELOVL6) and squalene epoxidase (SQLE) genes to affect triglyceride and total cholesterol content in the liver. 17ß-estradiol could significantly inhibit the expression of gga-miR-221-5p but promote the expression of ELOVL6 and SQLE genes. In conclusion, the highly conservative gga-miR-221-5p could directly target ELOVL6 and SQLE mRNAs to affect the level of intracellular triglyceride and total cholesterol. Meanwhile, 17ß-estradiol could repress the expression of gga-miR-221-5p but increase the expression of ELOVL6 and SQLE, therefore promoting the synthesis of intracellular triglyceride and cholesterol levels in the liver of egg-laying chicken.