Transcriptome dynamic landscape underlying the improvement of maize lodging resistance under coronatine treatment.

BACKGROUND: Lodging is one of the important factors causing maize yield. Plant height is an important factor in determining plant architecture in maize (Zea mays L.), which is closely related to lodging resistance under high planting density. Coronatine (COR), which is a phytotoxin and produced by the pathogen Pseudomonas syringae, is a functional and structural analogue of jasmonic acid (JA). RESULTS: In this study, we found COR, as a new plant growth regulator, could effectively reduce plant height and ear height of both hybrids (ZD958 and XY335) and inbred (B73) maize by inhibiting internode growth during elongation, thus improve maize lodging resistance. To study gene expression changes in internode after COR treatment, we collected spatio-temporal transcriptome of inbred B73 internode under normal condition and COR treatment, including the three different regions of internode (fixed, meristem and elongation regions) at three different developmental stages. The gene expression levels of the three regions at normal condition were described and then compared with that upon COR treatment. In total, 8605 COR-responsive genes (COR-RGs) were found, consist of 802 genes specifically expressed in internode. For these COR-RGs, 614, 870, 2123 of which showed expression changes in only fixed, meristem and elongation region, respectively. Both the number and function were significantly changed for COR-RGs identified in different regions, indicating genes with different functions were regulated at the three regions. Besides, we found more than 80% genes of gibberellin and jasmonic acid were changed under COR treatment. CONCLUSIONS: These data provide a gene expression profiling in different regions of internode development and molecular mechanism of COR affecting internode elongation. A putative schematic of the internode response to COR treatment is proposed which shows the basic process of COR affecting internode elongation. This research provides a useful resource for studying maize internode development and improves our understanding of the COR regulation mechanism based on plant height.

[Protective effects of Schizonepeta volatile oil on endotoxin poisoning induced by lipopolysaccharide in mice].

In order to study the protective effects of Schizonepeta volatile oil (Sto）on endotoxin poisoning mice, and the relatively content of each chemical osubstance in Schizonepeta volatile oil was measured using GC-MS. The mare C57BL/6J mice were randomly divided into five groups including the normal group, model group, dexamethasone group (5 mg•kg⁻¹), and Sto (0.226 and 0.452 g•kg⁻¹, respectively) groups. The dexamethasone group was given the drugs once time by intraperitoneal injection on the 5th day, while the other mice were given drugs by oral administration once a day for 5 days. Then, the normal group was injected with the saline and the other groups were injected LPS (15 mg•kg-1) after 30 minutes of the last administration. After LPS injection twelve hours, the blood, serum, and lung tissue of mice were collected. The IL-18, IL-1ß, IL-5, TNF-α, MCP-1, MIP-1ß, M-CSF, and GM-CSF were measured in serum by ELISA and Luminex Magpix. The white cell (WBC) and platelet (PLT) in blood were counted and lung, spleen, and thymus index were calculated. The lung histopathology was performed at the same time. The GC-MS results showed that the relative content of menthone and pulegone are 46.67% and 33.92%, respectively. The Sto (0.452 and 0.226 g•kg⁻¹, respectively) reduced the levels of IL-1ß, IL-5, TNF-α, MCP-1, MIP-1ß, and M-CSF in serum (P<0.01 or P<0.05). The 0.452 g•kg⁻¹ Sto also reduced the levels of IL-18 and GM-CSF in the serum (P<0.01 or P<0.05). And the 0.226 g•kg⁻¹ Sto showed good anti-inflammatory effects by reducing neutrophil infiltration in the lung tissue. But the Sto had no effect on the increasing of WBC, spleen and lung index as well as decreasing of PLT and thymus index. The results showed that Sto has a protective effect in LPS-induced exdotoxin poisoning mice, its mechanism is related to inhibit the release of varies of inflammatory cytokines and reduce the inflammation reaction.

[Evolution, characteristics and enlightenment of self-innovation of traditional Chinese medicine industry].

Traditional Chinese medicine industry is China's strategic emerging industry with great potential for self-innovation. Traditional Chinese medicine industry has successively experienced four stages which are the foundation (laying stage), the core status (establishing stage), the modern system (exploring stage), and the modernization system (constructing stage). Throughout the evolution of the self-innovation in traditional Chinese medicine industry, it presents distinct characteristics which we can explore the beneficial enlightenment.

Tumor necrosis therapy antibody interleukin-2 fusion protein elicits prolonged and targeted antitumor effects in vivo.

Interleukin-2 (IL-2) is one of the most successful cytokines applied in tumor immunotherapy because of its ability to stimulate potent cellular immune response. The life-threatening toxicity of vascular leak syndrome (VLS) associated with the high-dose IL-2 treatment regimen has limited its use in tumor immunotherapy. To reverse this situation, a tumor-targeted fusion protein, recombinant human TNT-IL2 (rhTNT-IL2), was generated with both the cytokine activity of IL-2 and the tumor-targeting ability of TNT antibody. TNT is a human tumor necrosis therapy monoclonal antibody capable of binding intracellular antigens which are accessible and abundant in necrotic regions of tumors. The immunotherapeutic potential of this fusion protein was tested in murine melanoma and lung cancer models, and tumor-bearing mice showed satisfied tumor regressions after rhTNT-IL2 immunotherapy. Immunohistochemical study showed a distinct penetration of IL-2 in tumors in mice treated with rhTNT-IL2, indicating its evident tumor-targeting activity. Moreover, the rhTNT-IL2 was well tolerated in cynomolgus monkeys in a 12-week long-term repeated toxicity study. These studies indicate that the targeting of IL-2 to necrotic areas of tumors might be a new approach for the immunotherapy of solid tumors.

Emotion-movement relationship: A study using functional brain network and cortico-muscular coupling.

BACKGROUND: Emotions play a crucial role in human communication and affect all aspects of human life. However, to date, there have been few studies conducted on how movements under different emotions influence human brain activity and cortico-muscular coupling (CMC). NEW METHODS: In this study, for the first time, electroencephalogram (EEG) and electromyogram physiological electrical signals were used to explore this relationship. We performed frequency domain and nonlinear dynamics analyses on EEG signals and used transfer entropy to explore the CMC associated with the emotion-movement relationship. To study the transmission of information between different brain regions, we also constructed a functional brain network and calculated various network metrics using graph theory. RESULTS: We found that, compared with a neutral emotional state, movements made during happy and sad emotions had increased CMC strength and EEG power and complexity. The functional brain network metrics of these three emotional states were also different. COMPARISON WITH EXISTING METHODS: Much of the emotion-movement relationship research has been based on subjective expression and external performance. Our research method, however, focused on the processing of physiological electrical signals, which contain a wealth of information and can objectively reveal the inner mechanisms of the emotion-movement relationship. CONCLUSIONS: Different emotional states can have a significant influence on human movement. This study presents a detailed introduction to brain activity and CMC.

Lignosulfonate Improves Photostability and Bioactivity of Abscisic Acid under Ultraviolet Radiation.

Abscisic acid (ABA), as a commonly used plant growth regulator, is easy to be degraded and lose its bioactivity under sunshine. To select an eco-friendly and efficient photoprotectant for the improvement of photostability and bioactivity of ABA when exposed to ultraviolet (UV) light, we tested the effects of three biodegradable natural-derived high polymers, sodium lignosulfonates 3A [molecular weight (MW) > 50000, with degree of sulfonation (DS) of 0.48] and NA (20000 < MW < 50000, with DS of 0.7) and calcium lignosulfonate CASA (MW < 20000, with DS of 0.7), on the photodegradation of ABA. Lignosulfonates 3A, NA, and CASA showed significant photostabilizing capability on ABA. Lignosulfonate 3A showed preferable photostabilizing effects on ABA compared to CASA, while NA showed an intermediate effect. That indicated that lignosulfonate with a high MW and low DS had a stronger UV absorption and the hollow aggregate micelles formatted by lignosulfonate protect ABA from UV damage. Approximately 50% more ABA was kept when 280 mg/L ABA aqueous solution was irradiated by UV light for 2 h in the presence of 2000 mg/L lignosulfonate 3A. The bioactivity on wheat (JIMAI 22) seed germination was greatly kept by 3A in comparison to that of ABA alone. The 300 times diluent of 280 mg/L ABA plus 2000 mg/L 3A after 2 h of irradiation showed 20.8, 19.3, and 9.3% more inhibition on shoot growth, root growth, and root numbers of wheat seed, separately, in comparison to ABA diluent alone. We conclude that lignosulfonate 3A was an eco-friendly and efficient agent to keep ABA activity under UV radiation. This research could be used in UV-sensitive and water-soluble agrichemicals and to optimize the application times and dosages of ABA products.

Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer.

PURPOSE: Tumor necrosis treatment (TNT) uses degenerating tumor cells and necrotic regions of tumors as targets for radioimmunotherapy. Previous studies in animal tumor models and clinical trials have demonstrated that when linked to the therapeutic radionuclide iodine-131, recombinant chimeric TNT antibody ((131)I-chTNT) can deliver therapeutic doses to tumors regardless of the location or type of malignancy. Therapeutic efficacy and toxicity of (131)I-chTNT in advanced lung cancer patients were studied in this pivotal registration trial. PATIENTS AND METHODS: Patients with advanced lung cancer were treated with systemic or intratumoral injection of (131)I-chTNT in eight oncology centers in China. The objective response rate (ORR) was assessed as the primary end point. RESULTS: All 107 patients who were entered onto the study and completed therapy had experienced treatment failure after prior radiotherapy or chemotherapy a mean of three times. The results showed an ORR of 34.6% (complete response, 3.7%; partial response, 30.8%; no change, 55.1%; and progressive disease, 10.3%) in all patients and 33% in 97 non-small-cell lung cancer patients. A biodistribution study demonstrated excellent localization of the radioactivity in tumors in both systemically and intratumorally injected patients. The most obvious adverse side effect was mild and reversible bone marrow suppression. CONCLUSION: Radioimmunotherapy with (131)I-chTNT was well tolerated and can be used systemically or locally to treat refractory tumors of the lung.

131I-chTNT radioimmunotherapy of 43 patients with advanced lung cancer.

UNLABELLED: The treatment of advanced lung cancer remains a major challenge in clinical medicine, justifying an urgent need for new therapeutic approaches. In a rather unique international collaboration, 43 patients with advanced lung cancer were treated using iodine-131-labeled tumor necrosis therapy chimeric antibody (131I-chTNT). METHODS: Patients were treated either with intravenous (i.v.) infusion (n = 22), intratumoral injection using a computer tomography (CT)-guided catheter (n = 16), or combination i.v. and intratumoral infusion (n = 5). All patients, regardless of route of administration, received 2 doses of 131I-chTNT on days 1 and 14. RESULTS: The results showed that of those patients receiving i.v. injection alone, 2 achieved partial response (PR) (9%), 16 had stable disease (73%), and 4 progressed (18%). Of those patients receiving intratumoral injection only, 1 had a complete response (CR) (6%), 8 achieved PR (50%), 7 had stable disease (44%), and none (0%) progressed. Finally, of those patients receiving both i.v. and intratumoral administration, 1 had a CR (20%), 1 achieved PR (20%), 2 had stable disease (40%), and 1 (20%) showed progression. CONCLUSIONS: These promising results demonstrate that sufficient doses of radiolabeled antibody can be safely delivered to tumors to cause significant therapeutic effects in advanced lung cancer.

Tumor cell membrane-bound heat shock protein 70 elicits antitumor immunity.

A novel membrane-bound heat shock protein 70 (mbHSP70) was expressed on the surface of the mouse mastocytoma cell line P815 to enhance immunogenicity of tumor cells. The in vivo effect of mbHSP70 was evaluated by comparing the growth of mbHSP70 cells to that of mock-transfected cells in DBA/2 mice. Fifty percent mice rejected mbHSP70 cells while 100% mice developed tumors in the counterparts. We then tested whether vaccination with these cells would elicit a protective antitumor response by injecting mice with either inactivated mbHSP70 cells or mock-transfected cells and challenging them with wild-type P815 cells. MbHSP70 cells-treated mice grew small tumors that soon disappeared in all animals. In contrast, 60% of animals receiving the mock-transfected cells vaccine grew large tumors and died. Lymphocytes from mbHSP70-vaccinated mice were able to kill wild-type P815 cells, suggesting that the antitumor response involved CTL. However, the activity of NK from mbHSP70 and mock-transfected cells vaccinated mice also increased. It implied that the non-specific immunity was also involved in tumor rejection. These findings indicate that the tumor cell membrane-bound HSP70 can be used as cancer vaccine to elicit protective antitumor immunity.

Pharmacokinetics and pharmacodynamics of recombinant human EPO-Fc fusion protein in vivo.

In this study, the in vivo pharmacokinetics and pharmacodynamics of a novel recombinant human erythropoietin (rhEPO) Fc fusion protein, rhEPO-Fc, were studied in both rodents and rhesus monkeys. Animal models of anemia induced by irradiation, cyclophosphamide and partial renal ablation were used to evaluate therapeutic effects of rhEPO-Fc. We have demonstrated that serum half-life of rhEPO-Fc was 29.5 to 38.9 h at doses of 8, 25, 80 µg/kg in rhesus monkeys and 35.5 to 43.5 h at doses of 16, 50, 160 µg/kg in rats. In anemia animal models, rhEPO-Fc dose-dependently (7.5-30.0 µg/kg in mice, 5.4-21.4 µg/kg in rats and 5.0-10.0 µg/kg in rhesus monkeys) increased reticulocyte level, followed by an increase of RBC count, hemoglobin and hematocrit levels. At reduced intervention frequency of weekly treatments, rhEPO-Fc showed similar hematopoietic effects as compared with rhEPO given three times a week. These results indicated that rhEPO-Fc could potentially be used in treatment of anemia and warrants future clinical trials.

Protective effects of Schizonepeta volatile oil on endotoxin poisoning induced by lipopolysaccharide in mice / 中国中药杂志

In order to study the protective effects of Schizonepeta volatile oil (Sto）on endotoxin poisoning mice, and the relatively content of each chemical osubstance in Schizonepeta volatile oil was measured using GC-MS. The mare C57BL/6J mice were randomly divided into five groups including the normal group, model group, dexamethasone group (5 mg•kg⁻¹), and Sto (0.226 and 0.452 g•kg⁻¹, respectively) groups. The dexamethasone group was given the drugs once time by intraperitoneal injection on the 5th day, while the other mice were given drugs by oral administration once a day for 5 days. Then, the normal group was injected with the saline and the other groups were injected LPS (15 mg•kg-1) after 30 minutes of the last administration. After LPS injection twelve hours, the blood, serum, and lung tissue of mice were collected. The IL-18, IL-1β, IL-5, TNF-α, MCP-1, MIP-1β, M-CSF, and GM-CSF were measured in serum by ELISA and Luminex Magpix. The white cell (WBC) and platelet (PLT) in blood were counted and lung, spleen, and thymus index were calculated. The lung histopathology was performed at the same time. The GC-MS results showed that the relative content of menthone and pulegone are 46.67% and 33.92%, respectively. The Sto (0.452 and 0.226 g•kg⁻¹, respectively) reduced the levels of IL-1β, IL-5, TNF-α, MCP-1, MIP-1β, and M-CSF in serum (P<0.01 or P<0.05). The 0.452 g•kg⁻¹ Sto also reduced the levels of IL-18 and GM-CSF in the serum (P<0.01 or P<0.05). And the 0.226 g•kg⁻¹ Sto showed good anti-inflammatory effects by reducing neutrophil infiltration in the lung tissue. But the Sto had no effect on the increasing of WBC, spleen and lung index as well as decreasing of PLT and thymus index. The results showed that Sto has a protective effect in LPS-induced exdotoxin poisoning mice, its mechanism is related to inhibit the release of varies of inflammatory cytokines and reduce the inflammation reaction.

Immunogenicity of Iodine 131 chimeric tumor necrosis therapy monoclonal antibody in advanced lung cancer patients.

PURPOSE: Iodine-131 radiolabeled chimeric tumor necrosis therapy monoclonal antibody ((131)I-TNT) has been approved for the treatment of advanced lung cancer in China. In the present study, the immunogenicity of TNT was studied in advanced lung cancer patients using BIACORE and enzyme linked immunosorbent assay (ELISA) methods. EXPERIMENTAL DESIGN: Serum samples from 78 advanced lung cancer patients were analyzed for antibody development to TNT after systemic or intratumoral administration of two doses of (131)I-TNT. Patients' sera were obtained before, and 2 weeks and 2 months after (131)I-TNT radioimmunotherapy. RESULTS: Four of 78 lung cancer patients (4/78 or 5.13%) developed antibodies to TNT as measured by ELISA method, and 7 of 78 patients (8.97%) development anti-TNT antibody as measured by BIACORE biosensor after 2 doses of (131)I-TNT administration (P > 0.05). All the 4 ELISA-positive patients were also BIACORE-positive. Among the 7 BIACORE-positive patients, 5 (of 42, 11.9%) patients receiving intravenous TNT injection developed antibodies to TNT, and 2 (of 36, 5.56%) patients, receiving intratumoral therapy developed antibodies to TNT. The route of administration of the radiolabeled TNT antibody was not a statistically significant factor in the incidence of anti-TNT antibody. Detailed BIACORE serological analysis showed that the induced antibodies were mostly of the IgG1 subclass. CONCLUSIONS: (131)I-TNT was immunogenic in only a small minority of advanced lung cancer patients (8.97%). The route of administration did not statistically influence the incidence of anti-TNT antibody after TNT radioimmunotherapy in lung cancer patients.