Mutant IAA21 genes from Dendrocalamus sinicus Chia et J. L. Sun inhibit stem and root growth in transgenic tobacco by interacting with ARF5.

Woody bamboos are important resource of industrial fibres. Auxin signaling plays a key role in multiple plant developmental processes, as yet the role of auxin/indole acetic acid (Aux/IAA) in culm development of woody bamboos has not been previously characterized. Dendrocalamus sinicus Chia et J. L. Sun is the largest woody bamboo documented in the world. Here, we identified two alleles of DsIAA21 gene (sIAA21 and bIAA21) from the straight- and bent-culm variants of D. sinicus, respectively, and studied how the domains I, i, and II of DsIAA21 affect the gene transcriptional repression. The results showed that bIAA21 expression was rapidly induced by exogenous auxin in D. sinicus. In transgenic tobacco, sIAA21 and bIAA21 mutated in domains i, and II significantly regulated plant architecture and root development. Stem cross sections revealed that parenchyma cells were smaller in transgenic plants than that in wild type plants. Domain i mutation changed the leucine and proline at position 45 to proline and leucine (siaa21L45P and biaa21P45L) strongly repressed cell expansion and root elongation by reducing the gravitropic response. Substitution of isoleucine with valine in domain II of the full length DsIAA21 resulted in dwarf stature in transgenic tobacco plants. Furthermore, the DsIAA21 interacted with auxin response factor 5 (ARF5) in transgenic tobacco plants, suggesting that DsIAA21 might inhibit stem and root elongation via interacting with ARF5. Taken together, our data indicated that DsIAA21 was a negative regulator of plant development and suggested that amino acid differences in domain i of sIAA21 versus bIAA21 affected their response to auxin, and might play a key role in the formation of the bent culm variant in D. sinicus. Our results not only shed a light on the morphogenetic mechanism in D. sinicus, but also provided new insights into versatile function of Aux/IAAs in plants.

Evaluation of diagnostic and predictive values of the serum VEGF-A level and systemic immune-inflammation index in small cell lung cancer.

Purpose: To evaluate diagnostic and predictive values of the serum vascular endothelial growth factor-A (VEGF-A) level and systemic immune-inflammation index (SII) in small cell lung cancer (SCLC) patients. Methods: From January 2018 to April 2020, we prospectively enrolled 59 untreated SCLC patients in the study group and 50 non-neoplastic patients in the control group. Blood samples were collected at baseline, after the first two cycles of chemotherapy and at progression in the study group and at entry in the control group. Serum VEGF-A was measured by chemiluminescence, SII was calculated based on complete blood count results, and the relationship between the VEGF-A/SII and clinicopathological characteristics, chemotherapeutic efficacy and progression-free survival (PFS) of SCLC patients was analyzed. Results: Baseline serum VEGF-A was significantly higher in SCLC patients than in non-neoplastic patients (P<0.001), while baseline SII was not (P=0.114). There was no correlation between baseline VEGF-A and SII in SCLC patients (P=0.123); however, there was a significant correlation between baseline VEGF-A and disease stage and central nervous system (CNS) metastasis (P=0.021 and P=0.012, respectively), as well as between baseline SII and disease stage and liver metastasis (P=0.026 and P=0.018, respectively). Serum VEGF-A was significantly lower than the pretreatment level after 2 cycles of treatment (P=0.049) but was not different at progression (P=0.247). Baseline VEGF-A was correlated with the treatment response of first-line chemotherapy (P=0.001), while baseline SII was not (P=0.392). Kaplan-Meier survival analysis suggested that the PFS of first-line chemotherapy was significantly longer in the low-VEGF-A group at baseline than the high-VEGF-A group (11.37 vs. 6.17 months, P<0.001). There was a trend toward longer PFS of first-line chemotherapy in the low-SII group at baseline than the high-SII group, but the difference was not significant (12.10 vs. 9.10 months, P>0.050). Univariate and multivariate Cox regression analyses suggested that baseline VEGF-A (HR: 3.443, 95% CI: 1.330-8.908, P=0.011) was an independent prognostic factor for PFS in SCLC patients. Conclusions: Baseline serum VEGF-A and SII are associated with important clinicopathological characteristics of SCLC patients. VEGF-A, but not SII, has the ability of diagnosis and predicting first-line chemotherapeutic efficacy and prognosis in SCLC patients.

Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study.

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

[Effect of different types of moxibustion intervention on expression of inflammatory cytokines IL-1 and TNF-alpha in rabbits with rheumatoid arthritis].

OBJECTIVE: To observe the effect of different moxibustion intervention on expression of interleukin-1 (IL-l) and tumor necrosis factor-alpha (TNF-alpha) in the synovial fluid of hind-knee joint in rheumatoid arthritis (RA) rabbits. METHODS: Forty Japanese big-ear white rabbits (half male and half female) were randomized into normal control, RA model, direct-moxibustion, ginger-partitioned moxibustion and warm moxibustion groups (n= 8). RA model was established by injection of Freund's Complete Adjuvant (0. 5 mL/kg) into the articular cavities of the rabbits' bilateral hind-limbs. Moxibustion intervention was applied to unilateral "Shenshu" (BL 23) and "Zusanli"(ST 36) regions alternatively for 20 min from the 7th day on after modeling, once daily for 3 weeks except Sundays. The circumference of the hindlimb-knee joint was measured using a tape measure and the contents of IL-1 and TNF-alpha in the synovial fluid of articular cavities were detected by ELISA. RESULTS: In comparison with the normal control group, the circumference values of the bilateral hind-knee joints, and the contents of IL-1 and TNF-alpha in the synovial fluid of articular cavities in the model group were significantly increased (P<0. 01). After the moxibustion treatment, compared with the model group, the circumference values of the bilateral hind-knee joints, and IL-1 and TNF-alpha contents of the synovial fluid in the warm moxibustion, direct moxibustion and ginger-partitioned moxibustion groups were remarkably reduced (P<0.01, P<0.05). The effects of the ginger-partitioned group were significantly superior to those of both warm moxibustion and direct moxibustion groups in decreasing the swelled hind-knee joint circumference on day 21 after the treatment and down-regulating synovial fluid inflammatory cytokines IL-1 and TNF-alpha levels (P<0. 05). CONCLUSION: Warm, direct and ginger-separated moxibustion interventions all can reduce inflammatory reactions of the knee-joint and suppress inflammatory cytokine IL-1 and TNF-alpha levels of the synovial fluid in RA rabbits, which may contribute to its effect in improving RA in clinic. The therapeutic effect of ginger-partitioned muxibustion intervention is apparently better.