Natural variations of ZmSRO1d modulate the trade-off between drought resistance and yield by affecting ZmRBOHC-mediated stomatal ROS production in maize.

While crop yields have historically increased, drought resistance has become a major concern in the context of global climate change. The trade-off between crop yield and drought resistance is a common phenomenon; however, the underlying molecular modulators remain undetermined. Through genome-wide association study, we revealed that three non-synonymous variants in a drought-resistant allele of ZmSRO1d-R resulted in plasma membrane localization and enhanced mono-ADP-ribosyltransferase activity of ZmSRO1d toward ZmRBOHC, which increased reactive oxygen species (ROS) levels in guard cells and promoted stomatal closure. ZmSRO1d-R enhanced plant drought resilience and protected grain yields under drought conditions, but it led to yield drag under favorable conditions. In contrast, loss-of-function mutants of ZmRBOHC showed remarkably increased yields under well-watered conditions, whereas they showed compromised drought resistance. Interestingly, by analyzing 189 teosinte accessions, we found that the ZmSRO1d-R allele was present in teosinte but was selected against during maize domestication and modern breeding. Collectively, our work suggests that the allele frequency reduction of ZmSRO1d-R in breeding programs may have compromised maize drought resistance while increased yields. Therefore, introduction of the ZmSRO1d-R allele into modern maize cultivars would contribute to food security under drought stress caused by global climate change.

Inhibition of osteosarcoma cell proliferation in vitro and tumor growth in vivo in mice model by alstonine through AMPK-activation and PGC-1α/TFAM up-regulation.

Osteosarcoma, a leading malignant tumor of bones is diagnosed mostly in adolescents and young adults worldwide. The present study investigated alstonine as anti-osteosarcoma agent in vitro as well as in vivo and evaluated the underlying mechanism. Treatment with alstonine led to a significant (P<0.05) reduction in MG63 and U-2OS cell viability. Alstonine treatment of MG63 and U-2OS cells caused a significant reduction in colony formation compared to the control cells. Viability of osteoblasts was not affected by alstonine treatment in 1.25 to 20 µM concentration range. In alstonine treated MG63 and U-2OS cells apoptotic cells increased significantly (P<0.05) compared to the control cells. Moreover, in MG63 and U-2OS cells treatment with alstonine caused a prominent increase in expression of cleaved caspase-9, caspase-3, and PARP. Treatment of MG63 and U-2OS cells with alstonine caused a prominent increase in AMPKα (Thr172) phosphorylation and elevated the count of mtDNA copies compared to the untreated cells. Alstonine treatment of the cells caused a remarkable increase in expression of PGC-1α and TFAM proteins. Treatment of the mice with alstonine at 5 and 10 mg/kg doses for 30 days caused a significant (P<0.05) reduction in xenograft growth. Expression of PGC-1α and TFAM proteins in tumor tissues of the mice treated with alstonine was significantly (P<0.05) raised compared to the control group. Thus, alstonine inhibits osteosarcoma cell growth and activates apoptosis through AMPK dependent pathway. Therefore, alstonine may be considered for treatment of osteosarcoma as it effectively arrests tumor growth in mice.

Comparison of total disc arthroplasty and fusion in treatment of lumbar disc disease: A cohort study protocol.

BACKGROUND: In recent years, the clinical efficacy of spinal fusion (SF) or total disc arthroplasty (TDA) in the treatment of the degenerative lumbar disc disease is still controversial. The objective of this retrospective clinical trial was to investigate whether TDA was superior to the SF in the complication rates and clinical outcome scores. METHODS: This retrospective research was based on the Strengthening the Reporting of Observational studies in Epidemiology checklist. Internal clinical data sets for 2014 to 2018 were acquired and consolidated with the approval of the Institutional Review Committee of Shaoxing Hospital of Zhejiang University. Inclusion criteria in this present research included: low back pain without or with the leg pain for more than one year; failure of conservative treatment planned for more than three months; age was 25 to 60 years old; followed up for at least one year. The main outcome measure was disability and pain measured via the Norwegian version of Oswestry disability index 2.0. The other clinical outcomes included Short-Form Health Survey, reoperations, duration of surgery, complications, hospital stay length, as well as the blood loss. The significance was set at 0.05 level with the confidence intervals of 95%. The software package of SPSS (version 21.0; SPSS Inc, Chicago, IL, USA) was applied for all the analyses of statistics. RESULTS: The null hypothesis is that there is no significant difference in outcomes between TDA and SF in the treatment of degenerative lumbar disc disease. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5847).

The constitutive expression of alfalfa MsMYB2L enhances salinity and drought tolerance of Arabidopsis thaliana.

MYB-type transcription factors are known to participate in the response of plants to a number of stress agents. MsMYB2L is an alfalfa member of this large gene family. Its transcription in alfalfa seedlings was found to be rapidly and strongly induced by salinity, moisture deficiency and exogenously supplied abscisic acid. An analysis based on a yeast one hybrid assay indicated that its product is able to activate transcription, consistent with its function as a transcription factor. When the gene was constitutively expressed in Arabidopsis thaliana, both germination and seedling growth were more sensitive to ABA treatment than wild type, and growth was less strongly compromised by salinity and moisture deficiency stress, presumably as a result of the induction of certain stress-related genes active in ABA-dependent pathways. The transgenic seedlings' enhanced the synthesis of many osmotic regulatory substances such as proline and soluble sugar, and decreased the lipid peroxidation. In all, MsMYB2L represents a potential candidate gene for manipulating the salinity and drought tolerance of alfalfa.

Hypoxia-inducible factor-lα mediates aggrecan and collagen Π expression via NOTCH1 signaling in nucleus pulposus cells during intervertebral disc degeneration.

Although hypoxia-inducible factor-lα (HIF-lα) has been reported to have an important role in the metabolism and synthesis of the extracellular matrix (ECM) of nucleus pulposus cells (NPCs), the underlying mechanism has not been fully clarified. Here, we show for the first time that NOTCH1 expression is decreased in NPs isolated from degenerated human intervertebral discs (IVDs), as well as in the NPs of NP-specific HIF-1α-/- mice. Our study reveals that overexpression of HIF-1α leads to increased expression of NOTCH1, the NOTCH1 ligand JAGGED1, and its target gene hairy and enhancer of split-1 (HES1), while also upregulating collagen Π and aggrecan expression in human NPCs. Importantly, these changes in expression are significantly suppressed by the NOTCH1 inhibitor DAPT. In parallel with changes in collagen Π and aggrecan expression, inhibition of the HIF-1α-NOTCH1 pathway altered ECM turnover by suppressing expression of the matrix metalloproteinases MMP1 and MMP13, while increasing the expression of tissue inhibitor of metalloproteinase-1 (TIMP1). Lastly, activation of NOTCH1 via JAGGED1 in human NPCs isolated from degenerated IVDs restored collagen Π and aggrecan expression. Therefore, our study shows that HIF-1α regulates collagen Π and aggrecan expression through NOTCH1 signaling and implicate NOTCH1 as a potential therapeutic target in disc degeneration.