A programmable targeted protein-degradation platform for versatile applications in mammalian cells and mice.

Myriad physiological and pathogenic processes are governed by protein levels and modifications. Controlled protein activity perturbation is essential to studying protein function in cells and animals. Based on Trim-Away technology, we screened for truncation variants of E3 ubiquitinase Trim21 with elevated efficiency (ΔTrim21) and developed multiple ΔTrim21-based targeted protein-degradation systems (ΔTrim-TPD) that can be transfected into host cells. Three ΔTrim-TPD variants are developed to enable chemical and light-triggered programmable activation of TPD in cells and animals. Specifically, we used ΔTrim-TPD for (1) red-light-triggered inhibition of HSV-1 virus proliferation by degrading the packaging protein gD, (2) for chemical-triggered control of the activity of Cas9/dCas9 protein for gene editing, and (3) for blue-light-triggered degradation of two tumor-associated proteins for spatiotemporal inhibition of melanoma tumor growth in mice. Our study demonstrates that multiple ΔTrim21-based controllable TPD systems provide powerful tools for basic biology research and highlight their potential biomedical applications.

AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation.

Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAVMUSE) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (PCRE). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAVMUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAVMUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone-after only one injection of AAVMUSE-can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.

Di-(2-ethylhexyl) phthalate (DEHP) promoted hepatic lipid accumulation by activating Notch signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500 mg/kg/d) for 8 weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200 µM) for 24 h. About 50 µM DAPT and 100 µg/mL Aspirin were used to inhibit Notch pathway and prevent inflammation, respectively. Real-Time PCR was performed to detect the mRNA expression, western blot and immunofluorescence were used to detect the protein expression. Lipids and inflammatory factors levels were determined by commercial kits. The results showed that DEHP/MEHP promoted the expression of Notch pathway molecules and lipids accumulation in rat livers/BRL-3A cells. The up-regulated Notch receptors were correlated with the TG levels in the rat liver. MEHP increased the levels of IL-8 and IL-1ß. The lipids levels were reduced after anti-inflammation. The inhibition of Notch pathway reversed the elevation of inflammation and lipid accumulation caused by MEHP. In conclusion, this study demonstrated that DEHP/MEHP led to lipid accumulation in hepatocytes by up-regulating Notch pathway and the inflammation might play a key role in the process.

Nanoplastics and Microplastics May Be Damaging Our Livers.

Plastics in the environment can be degraded and even broken into pieces under the action of natural factors, and the degraded products with a particle size of less than 5 mm are called microplastics (MPs). MPs exist in a variety of environmental media that come into contact with the human body. It can enter the body through environmental media and food chains. At present, there are many studies investigating the damage of MPs to marine organisms and mammals. The liver is the largest metabolizing organ and plays an important role in the metabolism of MPs in the body. However, there is no available systematic review on the toxic effects of MPs on the liver. This paper summarizes the adverse effects and mechanisms of MPs on the liver, by searching the literature and highlighting the studies that have been published to date, and provides a scenario for the liver toxicity caused by MPs.

Effect of Acute Cold Exposure on Energy Metabolism and Activity of Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis.

Background: The benefit of cold exposure for humans against obesity has brought the energy metabolism and activity of brown adipose tissue (BAT) induced by cold into focus. But the results are inconsistent. This review is aimed to systematically explore the effect of cold exposure on the activity of BAT and energy metabolism in humans. Methods: We searched relevant papers that were published from 1990 to 2021 and were cited in PubMed Central, Web of science, Embase and Cochrane Library databases to conduct this systematic review and meta-analysis. Energy metabolism, BAT volume, BAT activity and non-esterified fatty acids (NEFA) data reported in eligible researches were extracted. Meta-analysis was applied to combine the mean difference or standard mean difference with their 95% confidence intervals (95%CI). RevMan 5.3 software was used for meta-analysis and evaluating the risk of bias. Stata 16.0 was used for evaluating the publication bias. Results: Ten randomized controlled trials were included in meta-analysis. Compared with human exposed in room temperature at 24°C, the energy expenditure (EE) was increased after acute cold exposure at 16∼19°C (Z = 7.58, p < 0.05, mean different = 188.43kal/d, 95% CI = 139.73-237.13); BAT volume (Z = 2.62, p < 0.05; standard mean different = 0.41, 95% CI = 0.10-0.73); BAT activity (Z = 2.05, p = 0.04, standard mean difference = 1.61, 95% CI = 0.07-3.14) and the intake of BAT NEFA (Z = 2.85, p < 0.05; standard mean different = 0.53, 95% CI = 0.17-0.90) also increased. Conclusion: Acute cold exposure could improve the energy expenditure and BAT activity in adults, which is beneficial for human against obesity.

The Relationship Between Colorectal Polyps and Serum Lipid Levels: A Systematic Review and Meta-analysis.

Colorectal polyp has been considered as the precancerous lesion of colorectal cancer, to which serum lipid levels are closely related. At present, there is no consensus on the relationship between colorectal polyps and serum lipid levels. We performed a meta-analysis to explore the effects of lipid levels on colorectal polyps. Relevant articles published from 2000 to 2020 were searched in PubMed, Web of Science, EMBASE, and Cochrane Library databases. The mean value and SD of serum lipid indexes and body mass index in colorectal polyps groups and control groups were extracted from the included articles. Combined weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated to assess the effect size of serum lipid levels on colorectal polyps. The publication bias of the included studies were assessed based on the Egger test. Thirty-seven articles containing 19,464 cases and 63,979 controls were included. There were no significant publication bias. The levels of high-density lipoprotein cholesterol in the cases were lower than those in the controls (WMD: -2.589 mg/dL, 95% CI: -3.273, -1.906). While the levels of triglyceride (WMD: 16.933 mg/dL, 95% CI: 13.131, 20.736), total cholesterol (WMD: 5.561 mg/dL, 95% CI: 3.477, 7.645), low-density lipoprotein cholesterol (WMD: 3.109 mg/dL, 95% CI: 0.859, 5.359) and body mass index (WMD: 0.747 mg/dL, 95% CI: 0.588, 0.906) were higher in the cases. Colorectal polyps were associated with serum lipid levels and obesity. Hyperlipidemia and obesity may be the risk factors for colorectal polyps.

Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control.

Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-(l-lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled "living cell factory" platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery.

A far-red light-inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation.

The CRISPR-Cas12a has been harnessed as a powerful tool for manipulating targeted gene expression. The possibility to manipulate the activity of CRISPR-Cas12a with a more precise spatiotemporal resolution and deep tissue permeability will enable targeted genome engineering and deepen our understanding of the gene functions underlying complex cellular behaviors. However, currently available inducible CRISPR-Cas12a systems are limited by diffusion, cytotoxicity, and poor tissue permeability. Here, we developed a far-red light (FRL)­inducible CRISPR-Cas12a (FICA) system that can robustly induce gene editing in mammalian cells, and an FRL-inducible CRISPR-dCas12a (FIdCA) system based on the protein-tagging system SUperNova (SunTag) that can be used for gene activation under light-emitting diode­based FRL. Moreover, we show that the FIdCA system can be deployed to activate target genes in mouse livers. These results demonstrate that these systems developed here provide robust and efficient platforms for programmable genome manipulation in a noninvasive and spatiotemporal fashion.

Role of miR-145-5p/ CD40 in the inflammation and apoptosis of HUVECs induced by PM2.5.

Fine particulate matter (PM2.5) exposure can cause the injury of vascular endothelial cells by inflammatory response. CD40 works in inflammation of endothelial cells and it may be regulated by the miRNAs. This study aimed to clarify the role and mechanism of CD40 and miR-145-5p in PM2.5-induced injury of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with different concentrations of PM2.5 exposure (0, 100, 200, 400 µg/mL) for 24 h. The si-RNA was used for CD40 gene silencing (0, 200 µg/mL PM2.5, siRNA-CD40 and siRNA-CD40 + 200 µg/mL PM2.5). Mimics was used for overexpression of miR-145-5p (0, 200 µg/mL PM2.5, mimics and mimics+200 µg/mL PM2.5). The cell viability of HUVECs was detected with Cell Counting Kit8 (CCK8) kit. The level of cell apoptosis was detected by flow cytometry. The inflammation-related factor including interleukin-1ß (IL-1ß), interleukin-18 (IL-18), tumor necrosis factor α (TNF-α) and C1q complement/tumor necrosis factor (TNF)-associated proteins9 (CTRP9) were tested with enzyme-linked immunosorbent assay (ELISA) kits. The mRNA and protein expression levels of CD40, CD40L, caspase1, NLRP3 (Nod-like receptor family pyrin domain-containing 3) and IKKB were detected with quantitative real-time PCR (qRT-PCR), Western blot and Immunofluorescence. Compared with the control group, the cell viability of HUVECs exposed to PM2.5 was significantly decreased (p < 0.05); the levels of IL-Iß and TNF-α were significantly increased, while the level of CTRP9 was significantly decreased (p < 0.05). The proportion of apoptotic cells was increased after being treated with PM2.5 (p < 0.05). Besides, the mRNA and protein levels of CD40, CD40L, IKKB, NLRP3 and caspase1 were increased comparing with the control group (p < 0.05). After CD40 silencing, the condition of inflammation and apoptosis in HUVECs exposed to PM2.5 was alleviated, and the expression levels of CD40L, IKKB, NLRP3 and caspase1 were significantly decreased (p < 0.05). Furthermore, miR-145-5p was significantly down-regulated after exposure to 200µg/mL PM2.5 (p < 0.05). After over-expression of miR-145-5p, the expression level of CD40 was decreased (p < 0.05). Taken together, PM2.5 can cause inflammation and apoptosis of HUVECs via the activation of CD40, which can be regulated by miR-145-5p. Over-expression of miR-145-5p can down-regulate CD40, further inhibiting the inflammation and apoptosis of HUVECs induced by PM2.5.

Relationships between di-(2-ethylhexyl) phthalate exposure and lipid metabolism in adolescents: Human data and experimental rat model analyses.

In recent years, the incidence of lipid metabolism disorders in adolescents has gradually increased, and the effects of DEHP on lipid metabolism have received widespread attention. In this study, 463 adolescents aged 16-19 years were enrolled as subjects. This study analyzed the associations between the urinary levels of DEHP metabolites (MEHP, MEOHP, MEHHP, MECPP, MCMHP, and ∑DEHP) and BMI, WHR, WtHR, VAI, LAP, the plasma levels of lipids (TC, TG, HDL-C, and LDL-C), and the peripheral blood leukocyte mRNA levels of SREBP-2, SR-BI, LDLR, and NR1H3. Animal experiments were performed to confirm and expand findings. Wistar rats were administered DEHP at 0, 5, 50, and 500 mg/kg/d for 8 weeks. The serum and liver levels of TC, TG, HDL-C, and LDL-C, and the liver mRNA and protein levels of SREBP-2, SR-BI, LDLR, and NR1H3 were measured. The results showed that WHR, VAI, and LAP were significantly positively associated with the urinary levels of MECPP and ∑DEHP; the plasma HDL-C level was significantly negatively associated with the levels of MECPP, MCMHP and ∑DEHP; the peripheral blood leukocyte mRNA levels of SREBP-2, NR1H3, and LDLR were significantly positively correlated with the MCMHP level; and the SR-BI mRNA level was significantly positively correlated with the levels of MECPP and MCMHP in adolescents. Moreover, the results of animal experiments showed that DEHP exposure significantly increased the serum levels of TC, HDL-C, and LDL-C in 500 mg/kg/d group, as well as the liver levels of TC and HDL-C, up-regulated SREBP-2 mRNA and protein expression in 50 and 500 mg/kg/d groups. DEHP exposure significantly down-regulated SR-BI and NR1H3 protein expression in the liver of the 500 mg/kg/d group rats. Our findings indicate that DEHP exposure can affect lipid metabolism in adolescents by regulating the expression of lipid metabolism-related genes.

Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol.

Chimeric antigen receptor (CAR)-engineered T cell therapies have been recognized as powerful strategies in cancer immunotherapy; however, the clinical application of CAR-T is currently constrained by severe adverse effects in patients, caused by excessive cytotoxic activity and poor T cell control. Herein, we harnessed a dietary molecule resveratrol (RES)-responsive transactivator and a transrepressor to develop a repressible transgene expression (RESrep) device and an inducible transgene expression (RESind) device, respectively. After optimization, these tools enabled the control of CAR expression and CAR-mediated antitumor function in engineered human cells. We demonstrated that a resveratrol-repressible CAR expression (RESrep-CAR) device can effectively inhibit T cell activation upon resveratrol administration in primary T cells and a xenograft tumor mouse model. Additionally, we exhibit how a resveratrol-inducible CAR expression (RESind-CAR) device can achieve fine-tuned and reversible control over T cell activation via a resveratrol-titratable mechanism. Furthermore, our results revealed that the presence of RES can activate RESind-CAR T cells with strong anticancer cytotoxicity against cells in vitro and in vivo. Our study demonstrates the utility of RESrep and RESind devices as effective tools for transgene expression and illustrates the potential of RESrep-CAR and RESind-CAR devices to enhance patient safety in precision cancer immunotherapies.

MUC5B regulates the airway inflammation induced by atmospheric PM2.5 in rats and A549 cells.

Atmospheric PM2.5 can induce airway inflammation and mucin secretion. MUC5B is required for airway defense. However, the research on the role of MUC5B in airway inflammation induced by atmospheric PM2.5 remains limited. This study was designed to explore the role of MUC5B in airway inflammation induced by atmospheric PM2.5. In vivo, Wistar rats were exposed to 0, 1.5, 7.5, 37.5 mg/ kg PM2.5 saline suspension via intratracheal instillation. HE staining and AB-PAS staining were used to observe the airway inflammation and goblet cell hyperplasia. In vitro, normal A549 cells and MUC5B-knockdown A549 cells were exposed to 0, 100, 200 and 400 µg/mL PM2.5 for 6 h, 12 h, 24 h and 48 h. ELISA was used to measure the levels of TNF-α and IL-1ß in serum and bronchoalveolar lavage fluid of rats and in cell culture. Real time-PCR and ELISA were used to quantify the mRNA and protein levels of MUC5B in trachea and lung of rats and in A549 cells. PM2.5 could cause the infiltration of inflammatory cells and increase the mucus secretions and goblet cell metaplasia. MUC5B is related to rats' airway inflammation induced by PM2.5. A549 cells exposed to PM2.5 in higher concentration and longer time, the protein level of MUC5B was significantly increased, while the levels of IL-1ß, TNF-α and MUC5B mRNA were significantly decreased. Compared with normal A549 cells, the levels of IL-1ß and TNF-α were significantly higher in Muc5b-knockdown cells. Atmospheric PM2.5 can induce airway inflammation and mucin secretion. MUC5B played a critical role in controlling the inflammatory response induced by PM2.5.

A green tea-triggered genetic control system for treating diabetes in mice and monkeys.

Cell-based therapies are recognized as the next frontier in medicine, but the translation of many promising technologies into the clinic is currently limited by a lack of remote-control inducers that are safe and can be tightly regulated. Here, we developed therapeutically active engineered cells regulated by a control system that is responsive to protocatechuic acid (PCA), a metabolite found in green tea. We constructed multiple genetic control technologies that could toggle a PCA-responsive ON/OFF switch based on a transcriptional repressor from Streptomyces coelicolor We demonstrated that PCA-controlled switches can be used for guide RNA expression-mediated control of the CRISPR-Cas9 systems for gene editing and epigenetic remodeling. We showed how these technologies could be used as implantable biocomputers in live mice to perform complex logic computations that integrated signals from multiple food metabolites. Last, we used our system to treat type 1 and type 2 diabetes in mice and cynomolgus monkeys. This biocompatible and versatile food phenolic acid-controlled transgenic device opens opportunities for dynamic interventions in gene- and cell-based precision medicine.

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice.

BACKGROUND: Obesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice. METHODS: A total of 40 wild-type C57BL/6 male mice were divided into four groups (10 in each group): the standard chow diet (STD) group was fed a STD; the HFD group was fed a HFD; and the HFD-RES/L and HFD-RES/H groups were fed a HFD plus RES (200 and 400 mg/kg/day, respectively). The L and H in RES/L and RES/H stand for low and high, respectively. Glucose tolerance, insulin sensitivity, circulating inflammatory biomarkers and lipid profile were determined. Quantitative PCR and Western blot were used to determine the expression of CC-chemokine receptor 2 (CCR2), other inflammation markers, glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and pAkt/Akt and to assess targets of interest involving glucose metabolism and inflammation in visceral WAT. RESULTS: HFD increased the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and proinflammatory cytokines in serum, decreased the high-density lipoprotein cholesterol level in serum, and induced insulin resistance and WAT inflammation in mice. However, RES treatment alleviated insulin resistance, increased the expressions of pAkt, GLUT4 and IRS-1 in WAT, and decreased serum proinflammatory cytokine levels, macrophage infiltration and CCR2 expression in WAT. CONCLUSION: Our results indicated that WAT CCR2 may play a vital role in macrophage infiltration and the inflammatory response during the development of insulin resistance in HFD-induced obesity. These data suggested that administration of RES offers protection against abnormal glucose metabolism and inflammatory adaptations in visceral WAT in mice with HFD-induced obesity.

[Research progress of mammalian synthetic biology in biomedical field].

Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases. We introduce common tools and design principles of synthetic gene circuits, and then we demonstrate open-loop gene circuits induced by different trigger molecules used in disease diagnosis and close-loop gene circuits used for biomedical applications. Finally, we discuss the perspectives and potential challenges of synthetic biology for clinical applications.

Self-adjusting synthetic gene circuit for correcting insulin resistance.

By using tools from synthetic biology, sophisticated genetic devices can be assembled to reprogram mammalian cell activities. Here, we demonstrate that a self-adjusting synthetic gene circuit can be designed to sense and reverse the insulin-resistance syndrome in different mouse models. By functionally rewiring the mitogen-activated protein kinase (MAPK) signalling pathway to produce MAPK-mediated activation of the hybrid transcription factor TetR-ELK1, we assembled a synthetic insulin-sensitive transcription-control device that self-sufficiently distinguished between physiological and increased blood insulin levels and correspondingly fine-tuned the reversible expression of therapeutic transgenes from synthetic TetR-ELK1-specific promoters. In acute experimental hyperinsulinemia, the synthetic insulin-sensing designer circuit reversed the insulin-resistance syndrome by coordinating expression of the insulin-sensitizing compound adiponectin. Engineering synthetic gene circuits to sense pathologic markers and coordinate the expression of therapeutic transgenes may provide opportunities for future gene- and cell-based treatments of multifactorial metabolic disorders.

Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice.

With the increasingly dominant role of smartphones in our lives, mobile health care systems integrating advanced point-of-care technologies to manage chronic diseases are gaining attention. Using a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology, we have engineered a technological infrastructure enabling the smartphone-assisted semiautomatic treatment of diabetes in mice. A custom-designed home server SmartController was programmed to process wireless signals, enabling a smartphone to regulate hormone production by optically engineered cells implanted in diabetic mice via a far-red light (FRL)-responsive optogenetic interface. To develop this wireless controller network, we designed and implanted hydrogel capsules carrying both engineered cells and wirelessly powered FRL LEDs (light-emitting diodes). In vivo production of a short variant of human glucagon-like peptide 1 (shGLP-1) or mouse insulin by the engineered cells in the hydrogel could be remotely controlled by smartphone programs or a custom-engineered Bluetooth-active glucometer in a semiautomatic, glucose-dependent manner. By combining electronic device-generated digital signals with optogenetically engineered cells, this study provides a step toward translating cell-based therapies into the clinic.

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes.

Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics.

[Simulation research of respiratory monitoring with magnetic detection electrical impedance tomography].

In order to explore the feasibility of applying magnetic detection electrical impedance tomography(MDEIT) on respiratory monitoring, aiming at the forward problem of magnetic detection electrical impedance tomography, we calculated the electric potential and current density distribution inside the imaging object by using the finite element method. We then got magnetic induction intensity outside the object at the end of exhaling and inhaling according to Biot-Savart's law. The results showed that the magnetic induction intensity at the end of inhaling was 8.875%,less than that at the end of exhaling. By the simulation results, we could understand the difference of magnetic induction intensity value surrounding the lung at the end of exhaling and inhaling due to the change of lung volume and electrical conductivity distribution better. Our research laid the foundation for the late image reconstruction and clinical disease detection.

Physiological responses to Nilaparvata lugens in susceptible and resistant rice varieties: allocation of assimilates between shoots and roots.

Nilaparvata lugens (Stål) is a typical vascular feeder, primarily sucking the phloem sap of host plants. Its feeding on rice, Oryza sativa L., plants changes the pattern of allocation of assimilates between roots and shoots, and the root:shoot (R/S) ratio of assimilates is often measured as an index of physiological responses to N. lugens. The current study investigated changes in the R/S ratio of biomass, sucrose, and soluble sugar contents of rice plants in a susceptible variety (TN1) and a resistant variety (Xieyou 963). The results demonstrated that root and shoot biomasses in the two varieties linearly decreased with the increase of N. lugens infestation density. However, the relationship between changes in the R/ S ratio ofbiomass and N. lugens density differed between rice varieties, with the R/S increasing with infestation density in TN1 and decreasing in Xieyou 963. Sucrose and soluble sugar contents and their R/S values were also significantly different between the two varieties. Compared with the control that was not infested by N. lugens, the R/S values of sucrose and soluble sugar at 3 days after infestation (DAI) increased but decreased at 6 DAI in TN1. The R/S values of sucrose and soluble sugar were higher at 6 DAI than those at 3 DAI in TN1, whereas these values were lower at 6 DAI than at 3 DAI in Xieyou 963. These contrasting results suggest that physiological responses to N. lugens infestation differ between the susceptible and tolerant rice varieties.