Hydrogen sulfide alleviates osmotic stress-induced root growth inhibition by promoting auxin homeostasis.

Hydrogen sulfide (H2 S) promotes plant tolerance against various environmental cues, and d-cysteine desulfhydrase (DCD) is an enzymatic source of H2 S to enhance abiotic stress resistance. However, the role of DCD-mediated H2 S production in root growth under abiotic stress remains to be further elucidated. Here, we report that DCD-mediated H2 S production alleviates osmotic stress-mediated root growth inhibition by promoting auxin homeostasis. Osmotic stress up-regulated DCD gene transcript and DCD protein levels and thus H2 S production in roots. When subjected to osmotic stress, a dcd mutant showed more severe root growth inhibition, whereas the transgenic lines DCDox overexpressing DCD exhibited less sensitivity to osmotic stress in terms of longer root compared to the wild-type. Moreover, osmotic stress inhibited root growth through repressing auxin signaling, whereas H2 S treatment significantly alleviated osmotic stress-mediated inhibition of auxin. Under osmotic stress, auxin accumulation was increased in DCDox but decreased in dcd mutant. H2 S promoted auxin biosynthesis gene expression and auxin efflux carrier PIN-FORMED 1 (PIN1) protein level under osmotic stress. Taken together, our results reveal that mannitol-induced DCD and H2 S in roots promote auxin homeostasis, contributing to alleviating the inhibition of root growth under osmotic stress.

Salt stress-induced chloroplastic hydrogen peroxide stimulates pdTPI sulfenylation and methylglyoxal accumulation.

High salinity, an adverse environmental factor affecting about 20% of irrigated arable land worldwide, inhibits plant growth and development by causing oxidative stress, damaging cellular components, and disturbing global metabolism. However, whether and how reactive oxygen species disturb the metabolism of salt-stressed plants remain elusive. Here, we report that salt-induced hydrogen peroxide (H2O2) inhibits the activity of plastid triose phosphate isomerase (pdTPI) to promote methylglyoxal (MG) accumulation and stimulates the sulfenylation of pdTPI at cysteine 74. We also show that MG is a key factor limiting the plant growth, as a decrease in MG levels completely rescued the stunted growth and repressed salt stress tolerance of the pdtpi mutant. Furthermore, targeting CATALASE 2 into chloroplasts to prevent salt-induced overaccumulation of H2O2 conferred salt stress tolerance, revealing a role for chloroplastic H2O2 in salt-caused plant damage. In addition, we demonstrate that the H2O2-mediated accumulation of MG in turn induces H2O2 production, thus forming a regulatory loop that further inhibits the pdTPI activity in salt-stressed plants. Our findings, therefore, illustrate how salt stress induces MG production to inhibit the plant growth.

WRKY13 Enhances Cadmium Tolerance by Promoting D-CYSTEINE DESULFHYDRASE and Hydrogen Sulfide Production.

Hydrogen sulfide (H2S), a plant gasotransmitter, functions in the plant response to cadmium (Cd) stress, implying a role for cysteine desulfhydrase in producing H2S in this process. Whether d -CYSTEINE DESULFHYDRASE (DCD) acts in the plant Cd response remains to be identified, and if it does, how DCD is regulated in this process is also unknown. Here, we report that DCD-mediated H2S production enhances plant Cd tolerance in Arabidopsis (Arabidopsis thaliana). When subjected to Cd stress, a dcd mutant accumulated more Cd and reactive oxygen species and showed increased Cd sensitivity, whereas transgenic lines overexpressing DCD had decreased Cd and reactive oxygen species levels and were more tolerant to Cd stress compared with wild-type plants. Furthermore, the expression of DCD was stimulated by Cd stress, and this up-regulation was mediated by a Cd-induced transcription factor, WRKY13, which bound to the DCD promoter. Consistently, the higher Cd sensitivity of the wrky13-3 mutant was rescued by the overexpression of DCD Together, our results demonstrate that Cd-induced WRKY13 activates DCD expression to increase the production of H2S, leading to higher Cd tolerance in plants.

Auxin abolishes SHI-RELATED SEQUENCE5-mediated inhibition of lateral root development in Arabidopsis.

Lateral roots (LRs), which form in the plant postembryonically, determine the architecture of the root system. While negative regulatory factors that inhibit LR formation and are counteracted by auxin exist in the pericycle, these factors have not been characterised. Here, we report that SHI-RELATED SEQUENCE5 (SRS5) is an intrinsic negative regulator of LR formation and that auxin signalling abolishes this inhibitory effect of SRS5. Whereas LR primordia (LRPs) and LRs were fewer and less dense in SRS5ox and Pro35S:SRS5-GFP plants than in the wild-type, they were more abundant and denser in the srs5-2 loss-of-function mutant. SRS5 inhibited LR formation by directly downregulating the expression of LATERAL ORGAN BOUNDARIES-DOMAIN 16 (LBD16) and LBD29. Auxin repressed SRS5 expression. Auxin-mediated repression of SRS5 expression was not observed in the arf7-1 arf19-1 double mutant, likely because ARF7 and ARF19 bind to the promoter of SRS5 and inhibit its expression in response to auxin. Taken together, our data reveal that SRS5 negatively regulates LR formation by repressing the expression of LBD16 and LBD29 and that auxin releases this inhibitory effect through ARF7 and ARF19.

Emergence of human infection with Jingmen tick virus in China: A retrospective study.

BACKGROUND: A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans. METHODS: We obtained skin-biopsy, blood and serum samples from patients with tick bites, and used high-throughput sequencing, in situ hybridisation, and serologic testing to diagnose and ascertain the cases of JMTV infection. FINDINGS: A JMTV strain was isolated from the tick Amblyomma javanense into an embryo-derived tick cell line. We obtained sustained passage of JMTV, and revealed that it was able to accumulate in salivary glands of experimentally infected ticks. Four JMTV-infected patients were identified by high-throughput sequencing of skin biopsies and blood samples. The virus replication in skin tissue was visualised by in situ hybridisation. The four patients all had an itchy or painful eschar at the site of tick bite, with or without lymphadenopathy. Immunohistochemical examination revealed remarkable local inflammation manifested as infiltration by neutrophils. Eight patients were identified by serological testing and showed more severe clinical manifestations. Two Ixodes persulcatus ticks detached from patients were positive for JMTV. All JMTV strains identified in this study formed a well-supported sub-lineage, distinct from those previously reported in China. Interpretation The public significance of JMTV should be highly concerning due to its potential pathogenicity for humans and efficient transmission by potential ticks. FUND: China Natural Science Foundation, State Key Research Development Programme, and United Kingdom Biotechnology and Biological Sciences Research Council.

[Significance of Simultaneous Analysis of Bone Marrow Smear and Bone Marrow Biopsy in the Diagnosis of Lymphoma].

OBJECTIVE: To explore the value of bone marrow smear combined with biopsy in the diagnosis of lymphoma. METHODS: Clinical data of 50 cases of lymphoma from our hospital were analyzed retrospectively, and the results of the bone marrow smear and the bone marrow biopsy were compared simultaneously. RESULTS: The decision for the degree of bone marrow hyperplasia in bone marrow biopsy slice was superior to that in smear, and the active or highly active hyperplasia of nucleated cells were observed in all the bone marrow biopsies; the lymphomatic cells were observed in bone marrow smear of the 12 patients(24%), but the bone marrow biopsies showed a higher detection rate of lymphomatic cells 44% in 22 patients(P<0.05); The hyperplasia of bone marrow fibrous tissue, mainly mild to moderate, were the common in cases with bone marrow involvement and the severity of bone marrow fibrosis positively correlated with the number of lymphomatic cells. CONCLUSION: Biopsy combined with aspiration can improve the accuracy of diagnosis in lymphoma with bone marrow involvement.

Reactive oxygen species mediated T lymphocyte abnormalities in an iron-overloaded mouse model and iron-overloaded patients with myelodysplastic syndromes.

The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3+ T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes. In order to explore the mechanism, male C57Bl/6 mice were intraperitoneally injected with iron dextran at a dose of 250 mg/kg every 3 days for 4 weeks to establish an iron-overloaded mouse model and the blood of each mouse was collected for the analysis of the T lymphocyte subsets and T cell apoptosis. The results showed that iron overload could reduce the percentage of CD3+ T cells and the ratio of Th1/Th2 and Tc1/Tc2 but increase the percentage of regulatory T (Treg) cells and the ratio of CD4/CD8. We also found that iron overload induced the apoptosis of T lymphocytes and increased its ROS level. Furthermore, these effects could be partially recovered after treating with antioxidant N-acetyl-L-cysteine (NAC) or iron chelator deferasirox (DFX). Taken together, these observations indicated that iron overload could selectively affect peripheral T lymphocytes and induce an impaired cellular immunity by increasing ROS level.

A role for CK2 ß subunit 4 in the regulation of plant growth, cadmium accumulation and H2O2 content under cadmium stress in Arabidopsis thaliana.

Protein kinase CK2, which consists of two α and two ß subunits, plays an essential role in plant development and is implicated in plant responses to abiotic stresses, including salt and heat. However, the function of CK2 in response to heavy metals such as cadmium (Cd) has not yet been established. In this study, the transgenic line CKB4ox, which overexpresses CKB4 encoding the CK2ß subunit and has elevated CK2 activity, was used to investigate the potential role of CK2 in response to Cd stress in Arabidopsis thaliana. Under Cd stress, CKB4ox showed reduced root growth and biomass accumulation as well as decreased chlorophyll and proline contents compared with wild type. Furthermore, increased Cd accumulation and a higher H2O2 content were found in CKB4ox, possibly contributing to the inhibition of CKB4ox growth under Cd stress. Additionally, altered levels of Cd and H2O2 were found to be associated with decreased expression of genes involved in Cd efflux, Cd sequestration and H2O2 scavenging. Taken together, these results suggest that elevated expression of CKB4 and increased CK2 activity enhance the sensitivity of plants to Cd stress by affecting Cd and H2O2 accumulation, including the modulation of genes involved in Cd transport and H2O2 scavenging. This study provides direct evidence for the involvement of plant CK2 in the response to Cd stress.

[Research progress of phytoestrogens-like chemical constituents in natural medicines].

Phytoestrogens, which can bind with estrogen receptor and produce estrogen-like effects, are a kind of nonsteroidal compound in plant. Phytoestrogens chemically include isoflavones, coumarins, lignans and other compounds. Phytoestrogens are selective estrogen receptor modulator, and have therapeutical effects on breast cancer, prostate cancer, cardiovascular disease, menopausal symptoms, osteoporosis and other disease, however, do not produce stimulatory hyperplasia effects on uterus, mammary glands and other tissues and organs with positive estrogen receptor. Long-term exposure or excessive use of phytoestrogens maybe affects male reproductive system and hematopoietic function of fetus. Some questions need to be further studied, such as evaluation criteria on biological activity, adverse effects, and action mechanism of phytoestrogen. This review covers plant sources, chemical structure, pharmacological activity and safety of phytoestrogens. It will provide a useful reference for intensive research and rational utilization the phytoestrogens.

Role of magnetic resonance imaging in the diagnosis of lesions in the sellar region.

OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) in the diagnosis of lesions in the sellar region. METHODS: The MRI data of 142 patients with surgically and pathologically proved lesions in the sellar region were retrospectively analyzed. Based on the MRI findings, the lesions were divided into pituitary adenoma and sellar region diseases except pituitary adenoma. According to the pathologic features, the sellar region diseases except pituitary adenoma were further divided into cystic lesions, parenchymatous lesions, and cystic and parenchymatous lesions. RESULTS: Of these 142 patients, pituitary adenoma was found in 30 cases, cystic lesions of sella region diseases except pituitary adenoma in 24. Further classification resulted in 66 cases of parenchymatous lesions and 22 cases of cystic and parenchymatous lesions. CONCLUSION: MRI-based classification of lesions in the sellar region is useful for the diagnosis and differential diagnosis.

Correlation of apparent diffusion coefficient with Ki-67 in the diagnosis of gliomas.

OBJECTIVE: To study the correlation between apparent diffusion coefficient (ADC) and Ki-67, a marker of tumor activity, in the diagnosis of gliomas. METHODS: Conventional magnetic resonance imaging (MRI), enhanced scanning, and diffusion-weighted imaging were performed in 76 patients with pathologically confirmed gliomas. The ADC values were measured at tumor parenchyma and the corresponding contralateral normal brain. The relatively ADC (rADC) values of the tumor parenchyma were calculated. The correlation of the ADC values with tumor grades was analyzed. The expression of Ki-67 was detected by immunohistochemical staining. The correlation between ADC value and Ki-67 in the diagnosis of gliomas was analyzed. RESULTS: The ADC values and rADC values of high-grade gliomas were significantly lower than those of low-grade gliomas. The ADC values of tumor parenchyma were inversely associated with the degree of malignancy of the gliomas (r=-0.898, r=-0.868; P<0.01). The expression of Ki-67 was significantly higher in high-grade gliomas than that in low-grade gliomas. The Ki-67 labeling index in grade 3 and 4 gliomas were (29.48 ± 19.78)% and (31.21 ± 17.50)%, respectively. Both of them were significantly higher than Ki-67 labeling index in low-grade (grade 1 and 2) gliomas [(2.33 ± 2.20)%] (P<0.01). Nevertheless, the Ki-67 labeling index showed no significant difference between grade 3 and 4 gliomas (P>0.05). The expression of Ki-67 was negatively correlated with the ADC values and rADC values in tumor parenchyma (r=-0.627, r=-0.607; P<0.01). CONCLUSION: The ADC and rADC values of tumor parenchyma can indirectly reflect the proliferation and malignancy of gliomas and therefore can be useful for the grading of glioma.

[Characteristics of T-cell lineage immunophenotype in 95 patients with acute lymphoid leukemia].

The objective of this study was to investigate the immunophenotype of T-lineage acute lymphoid leukemia (T-ALL) and to find valuable immunologic markers in T-ALL diagnosis and therapy. Four-color multiparametric flow cytometry(FCM) with CD45/SSC gating was used for immunophenotyping of 95 patients with newly diagnosed T-ALL. The results demonstrated that T-ALL occurred more frequently in males younger than 30 years of age and was usually accompanied by a high WBC count and tumor mass at diagnosis. Univariate analysis showed an influence on achievement of CR1 for age (< 30 years) but not for WBC count and tumor mass. According to WHO (2008) classification of tumors of haematopoietic and lymphoid tissues, 87 patients with confirmed subtype included 27 cases of Pro-T-ALL (31.0%), 31 cases of Pre-T-ALL (35.6%), 23 cases of cortical-T-ALL (26.4%), 6 cases of medullary-T-ALL (6.9%). CD34 expression in Pro-T-ALL was significantly higher than that of Pre-T-ALL (p = 0.001). After the first chemotherapy, the complete remission rate in Pro-T-ALL was statistically lower than that of Pre-T-ALL. Besides, the complete remission rate of immature T-ALL (including Pro-T-ALL and Pre-T-ALL) was also significantly lower than that in mature T-ALL (including cortical-T-ALL and medullary-T-ALL). Myeloid antigen (CD13, CD33) expression was associated with T-ALL subtype and treatment effect. While 66.7% of CD13(+) patients belonged to Pre-T-ALL, most (60.0%) of CD33(+) patients were classified into Pro-T-ALL; CD13 expression had no effect on CR1 rate whereas CD33(+) patients had worse treatment effect compared with CD33(-) groups (p = 0.001). Notably, the expression of CD117 reached up to 26.7% and the positive cases were primarily distributed in pro-T-TAll and pre-T-ALL. It is found that CD117 expression in CD34(-) group was homogeneous and CD117 expression level was less than 10% in 73.2% patients, but CD117 expression level in CD34(+) group was not homogenous, in which group the CD117 expression levels < 10%, 10% - 20% and > 20% were 44.2%, 17.3% and 38.5% respectively. As compared with CD34(-) group, the proportion of patients with CD117 expression levels < 10%, > 20% in CD34(+) group was higher, and there was significant difference between these 2 group. It is concluded that immunophenotype has great value in T-ALL diagnosis, classification as well as treatment. Flow cytometry provides access to find valuable immunologic markers for T-ALL biological research.

[Progress in biology of dendritic cells].

As the most potent antigen-presenting cells (APC), dendritic cells are important in launching both humoral and cellular immune responses against tumor. Although the high evaluation of DC in immunotherapy for cancer by means of DC vaccines, more studies have indicated DC is a heterogeneous population and proved that DC subsets are prominent determinants for the effectiveness of immune responses. Different DC subsets display different receptors and surface molecules, and express different sets of cytokines/chemokines, which result in distinct immunological outcomes. Clinical trials with ex vivo generated DC vaccines also manifest unexpected immunological tolerance as well as allergic response. It is essential to study the biological aspects of human DC subsets, which may be a key to the generation of novel DC-based vaccines. In this article, the progress of studies on biology of dendritic cells including their origins, differentiation, function and application of DC subsets is reviewed.

Nuclear translocation of dihydrofolate reductase is not a pre-requisite for DNA damage induced apoptosis.

Dihydrofolate reductase (DHFR) is a key enzyme for the synthesis of thymidylate, and therefore, of DNA. By applying subcellular proteomic analysis, we identified that the DHFR protein was translocated from cytoplasm into the nucleus when apoptosis was induced by NSC606985, a camptothecin analogue. The nuclear translocation of DHFR protein during apoptosis was independent of the cellular context, but it was more sensitive in cell death induction by DNA damaging agents such as doxorubicin, etoposide and ultraviolent radiation than endoplasmic reticulum stressors (brefeldin-A and tunicamycin) and anti-microtubule agents (paclitaxel and nocodozole). The addition of methotrexate almost completely blocked the nuclear translocation of DHFR protein. Further investigations showed that the nuclear translocation of DHFR was not a pre-requisite for DNA damage induced apoptosis. Therefore, its potential biological significance remains to be further explored.