OsJAZ10 negatively modulates the drought tolerance by integrating hormone signaling with systemic electrical activity in rice.

Jasmonic acid (JA) plays crucial functions in plant stress response, and the synergistic interaction between JA and abscisic acid (ABA) signaling is implicated to help plants adapt to environmental challenges, whereas the underlying molecular mechanism still needs to be revealed. Here, we report that OsJAZ10, a repressor in the JA signaling, represses rice drought tolerance via inhibition of JA and ABA biosynthesis. Function loss of OsJAZ10 markedly enhances, while overexpression of OsJAZ10ΔJas reduces rice drought tolerance. The osjaz10 mutant is more sensitive to exogenous ABA and MeJA, and produces higher levels of ABA and JA after drought treatment, indicating OsJAZ10 represses the biosynthesis of these two hormones. Mechanistic study demonstrated that OsJAZ10 physically interacts with OsMYC2. Transient transcriptional regulation assays showed that OsMYC2 activates the expression of ABA-biosynthetic gene OsNCED2, JA-biosynthetic gene OsAOC, and drought-responsive genes OsRAB21 and OsLEA3, while OsJAZ10 prevents OsMYC2 transactivation of these genes. Further, the electrophoretic mobility shift assay (EMSA) confirmed that OsMYC2 directly binds to the promoters of OsNCED2 and OsRAB21. Electrical activity has been proposed to activate JA biosynthesis. Interestingly, OsJAZ10 inhibits the propagation of osmotic stress-elicited systemic electrical signals, indicated by the significantly increased PEG-elicited slow wave potentials (SWPs) in osjaz10 mutant, which is in accordance with the elevated JA levels. Collectively, our findings establish that OsJAZ10 functions as a negative regulator in rice drought tolerance by repressing JA and ABA biosynthesis, and reveal an important mechanism that plants integrate electrical events with hormone signaling to enhance the adaption to environmental stress.

Rice OsPUB16 modulates the 'SAPK9-OsMADS23-OsAOC' pathway to reduce plant water-deficit tolerance by repressing ABA and JA biosynthesis.

Ubiquitin-mediated proteolysis plays crucial roles in plant responses to environmental stress. However, the mechanism by which E3 ubiquitin ligases modulate plant stress response still needs to be elucidated. In this study, we found that rice PLANT U-BOX PROTEIN 16 (OsPUB16), a U-box E3 ubiquitin ligase, negatively regulates rice drought response. Loss-of-function mutants of OsPUB16 generated through CRISPR/Cas9 system exhibited the markedly enhanced water-deficit tolerance, while OsPUB16 overexpression lines were hypersensitive to water deficit stress. Moreover, OsPUB16 negatively regulated ABA and JA response, and ospub16 mutants produced more endogenous ABA and JA than wild type when exposed to water deficit. Mechanistic investigations revealed that OsPUB16 mediated the ubiquitination and degradation of OsMADS23, which is the substrate of OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 9 (SAPK9) and increases rice drought tolerance by promoting ABA biosynthesis. Further, the ChIP-qPCR analysis and transient transactivation activity assays demonstrated that OsMADS23 activated the expression of JA-biosynthetic gene OsAOC by binding to its promoter. Interestingly, SAPK9-mediated phosphorylation on OsMADS23 reduced its ubiquitination level by interfering with the OsPUB16-OsMADS23 interaction, which thus enhanced OsMADS23 stability and promoted OsAOC expression. Collectively, our findings establish that OsPUB16 reduces plant water-deficit tolerance by modulating the 'SAPK9-OsMADS23-OsAOC' pathway to repress ABA and JA biosynthesis.

Advanced lung cancer patient with isolated heparin-induced thrombocytopenia: A case report.

RATIONALE: Heparin-induced thrombocytopenia (HIT), a potentially devastating form of drug-induced thrombocytopenia, occurs in patients receiving heparin for thrombosis prevention or treatment. An isolated HIT is characterized by decreased platelet counts without thrombosis, which are atypical and difficult to clinically find. SYMPTOMS AND CLINICAL FINDINGS: A 33-year-old female patient's admission examination revealed elevated D-dimer levels. After prophylactic anticoagulation using low-molecular weight heparin, her blood platelet counts were rapidly decreased, whereas her D-dimer levels increased, followed by presentations of chest tightness, abdominal pain, and skin itching without thrombosis. After excluding all the other causes of thrombocytopenia, HIT was suspected. Her 4Ts score was 5 points, and enzyme-linked immunoassay for platelet factor 4 (PF4)/heparin antibodies was positive, indicating isolated HIT. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient was diagnosed with advanced lung cancer presenting with isolated HIT. We immediately stopped low-molecular weight heparin and initiated rivaroxaban for anticoagulation. We administered thrombopoietin (TPO) and avatripopal maleate tablets to increase blood platelet counts, whereas intravenous immunoglobulin (IVIG) was administered to stimulate her immune system. The patient's thrombocytopenia was successfully treated without thrombosis and bleeding complications. LESSONS: Rivaroxaban is a potential option for tumor preventive anticoagulation and HIT treatment. Early HIT identification is necessary. After identification, the 4Ts score as well as PF4/heparin antibodies should be assessed and appropriate anticoagulants selected based on patients' conditions.

Synergy of purine-scaffold TLR7 agonist with doxorubicin on systemic inhibition of lymphoma in mouse model.

Chemo- and radio-therapy suffer from certain well-recognized drawbacks for lymphoma therapy. Passive immunotherapy with monoclonal antibody has improved outcome for patients with CD20+ B cell lymphoma, but not for T cell lymphoma. Therefore, novel treatment approaches are clearly required for T cell lymphoma. To date, the combined application targeting TLR7, 8 and 9 has established long-term antitumor immunity. We previously synthesized a purine-scaffold TLR7 agonist named GD5. Here, we report that the intratumoral administration of GD5 combined with doxorubicin (DOX), a conventional chemotherapeutic agent in T cell lymphoma. This combined treatment made mice to produce more cytokines in blood, and generate more potent cytotoxic T lymphocyte response, then result in effective eradication of both local and distant tumors in tumor-bearing mice. Our findings demonstrate the potential for enhancing the efficacy of the current standard DOX therapy through combination with TLR7 agonist GD5 to improve antitumor immune responses and provide durable remissions for T cell lymphoma.

Continuous hydrogenation of ethyl levulinate to γ-valerolactone and 2-methyl tetrahydrofuran over alumina doped Cu/SiO2 catalyst: the potential of commercialization.

Hydrogenation of levulinic acid (LA) and its esters to produce γ-valerolactone (GVL) and 2-methyl tetrahydrofuran (2-MTHF) is a key step for the utilization of cellulose derived LA. Aiming to develop a commercially feasible base metal catalyst for the production of GVL from LA, with satisfactory activity, selectivity, and stability, Al2O3 doped Cu/SiO2 and Cu/SiO2 catalysts were fabricated by co-precipitation routes in parallel. The diverse physio-chemical properties of these two catalysts were characterized by XRD, TEM, dissociative N2O chemisorptions, and Py-IR methods. The catalytic properties of these two catalysts were systematically assessed in the continuous hydrogenation of ethyl levulinate (EL) in a fixed-bed reactor. The effect of acidic property of the SiO2 substrate on the catalytic properties was investigated. To justify the potential of its commercialization, significant attention was paid on the initial activity, proper operation window, by-products control, selectivity, and stability of the catalyst. The effect of reaction conditions, such as temperature and pressure, on the performance of the catalyst was also thoroughly studied. The development of alumina doped Cu/SiO2 catalyst strengthened the value-chain from cellulose to industrially important chemicals via LA and GVL.