dsRNA-induced immunity targets plasmodesmata and is suppressed by viral movement proteins.

Emerging evidence indicates that in addition to its well-recognized functions in antiviral RNA silencing, dsRNA elicits pattern-triggered immunity (PTI), likely contributing to plant resistance against virus infections. However, compared to bacterial and fungal elicitor-mediated PTI, the mode-of-action and signaling pathway of dsRNA-induced defense remain poorly characterized. Here, using multicolor in vivo imaging, analysis of GFP mobility, callose staining, and plasmodesmal marker lines in Arabidopsis thaliana and Nicotiana benthamiana, we show that dsRNA-induced PTI restricts the progression of virus infection by triggering callose deposition at plasmodesmata, thereby likely limiting the macromolecular transport through these cell-to-cell communication channels. The plasma membrane-resident SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1, the BOTRYTIS INDUCED KINASE1/AVRPPHB SUSCEPTIBLE1-LIKE KINASE1 kinase module, PLASMODESMATA-LOCATED PROTEINs 1/2/3, as well as CALMODULIN-LIKE 41 and Ca2+ signals are involved in the dsRNA-induced signaling leading to callose deposition at plasmodesmata and antiviral defense. Unlike the classical bacterial elicitor flagellin, dsRNA does not trigger a detectable reactive oxygen species (ROS) burst, substantiating the idea that different microbial patterns trigger partially shared immune signaling frameworks with distinct features. Likely as a counter strategy, viral movement proteins from different viruses suppress the dsRNA-induced host response leading to callose deposition to achieve infection. Thus, our data support a model in which plant immune signaling constrains virus movement by inducing callose deposition at plasmodesmata and reveals how viruses counteract this layer of immunity.

Organic Electrochemical Transistor with MoS2 Nanosheets Modified Gate Electrode for Sensitive Glucose Sensing.

An organic electrochemical transistor (OECT) with MoS2 nanosheets modified on the gate electrode was proposed for glucose sensing. MoS2 nanosheets, which had excellent electrocatalytic performance, a large specific surface area, and more active sites, were prepared by liquid phase ultrasonic exfoliation to modify the gate electrode of OECT, resulting in a large improvement in the sensitivity of the glucose sensor. The detection limit of the device modified with MoS2 nanosheets is down to 100 nM, which is 1~2 orders of magnitude better than that of the device without nanomaterial modification. This result manifests not only a sensitive and selective method for the detection of glucose based on OECT but also an extended application of MoS2 nanosheets for other biomolecule sensing with high sensitivity.

Brachypodium distachyon is a suitable host plant for study of Barley yellow dwarf virus.

Barley yellow dwarf viruses (BYDVs) belong to the family Luteoviridae and cause disease in cereals. Because of the large and complex genome of cereal plants, it is difficult to study host-virus interactions. In order to establish a model host system for the studies on BYDVs, we examined the susceptibility of a monocot model plant, Brachypodium distachyon, to BYDV-GAV infection. Fourteen days after BYDV-GAV inoculation by aphid transmission, B. distachyon plants (inbred line Bd21-3) showed conspicuous disease symptoms such as leaf reddening, dwarfness and root stunting. Virus accumulation was detected in both shoots and roots using reverse transcription PCR and triple antibody sandwich ELISA. Compared with infected wheat plants, B. distachyon plants developed more severe disease symptoms and accumulated a higher level of BYDV-GAV. Under transmission electron microscope, we observed that virus particles accumulated in companion cells and BYDV-GAV infection was associated with the deformation of chloroplasts in the infected leaves of B. distachyon plants. Our results suggest that B. distachyon is a suitable and promising experimental model plant for the host-BYDV-GAV pathosystem and possibly for other BYDVs.

Study on the mechanism of photocatalytic degradation of patulin in simulated apple juice.

Patulin poses a potential risk to human health, and current methods for removing it have certain limits. Thus, the effective and secure technique for degrading patulin in juice is critical. In this study, a nitrogen-doped chitosan-TiO2 nanocomposite (N-TiO2 Nps) as a photocatalyst was employed to decompose patulin. Under the action of the photocatalyst, 500 µg/L patulin was completely degraded within 1 h in simulated juice. Quenching experiments identified superoxide and hydroxyl radicals as the dominant species responsible for patulin degradation. On the bases of liquid chromatography-mass spectrometry (LC-MS) and density functional theory (DFT) calculation, the reaction sites in patulin were predicted and a possible photodegradation pathway was proposed. The findings not only elucidated a new method for removing patulin but also provided a theoretical basis for scrutinizing the degradation mechanism of mycotoxins.

Dual RNA-Seq Reveals Temperature-Mediated Gene Reprogramming and Molecular Crosstalk between Grapevine and Lasiodiplodia theobromae.

High temperatures associated with a fluctuating climate profoundly accelerate the occurrence of a myriad of plant diseases around the world. A comprehensive insight into how plants respond to pathogenic microorganisms under high-temperature stress is required for plant disease management, whereas the underlying mechanisms behind temperature-mediated plant immunity and pathogen pathogenicity are still unclear. Here, we evaluated the effect of high temperature on the development of grapevine canker disease and quantified the contribution of temperature variation to the gene transcription reprogramming of grapevine and its pathogenic agent Lasiodiplodia theobromae using a dual RNA-seq approach. The results showed that both grapevine and the pathogen displayed altered transcriptomes under different temperatures, and even the transcription of a plethora of genes from the two organisms responded in different directions and magnitudes. The transcription variability that arose due to temperature oscillation allowed us to identify a total of 26 grapevine gene modules and 17 fungal gene modules that were correlated with more than one gene module of the partner organism, which revealed an extensive web of plant-pathogen gene reprogramming during infection. More importantly, we identified a set of temperature-responsive genes that were transcriptionally orchestrated within the given gene modules. These genes are predicted to be involved in multiple cellular processes including protein folding, stress response regulation, and carbohydrate and peptide metabolisms in grapevine and porphyrin- and pteridine-containing compound metabolisms in L. theobromae, implying that in response to temperature oscillation, a complex web of signaling pathways in two organism cells is activated during infection. This study describes a co-transcription network of grapevine and L. theobromae in the context of considering temperature variation, which provides novel insights into deciphering the molecular mechanisms underlying temperature-modulated disease development.

LtGAPR1 Is a Novel Secreted Effector from Lasiodiplodia theobromae That Interacts with NbPsQ2 to Negatively Regulate Infection.

The effector proteins secreted by a pathogen not only promote the virulence and infection of the pathogen but also trigger plant defense response. Lasiodiplodia theobromae secretes many effectors that modulate and hijack grape processes to colonize host cells, but the underlying mechanisms remain unclear. Herein, we report LtGAPR1, which has been proven to be a secreted protein. In our study, LtGAPR1 played a negative role in virulence. By co-immunoprecipitation, 23 kDa oxygen-evolving enhancer 2 (NbPsbQ2) was identified as a host target of LtGAPR1. The overexpression of NbPsbQ2 in Nicotiana benthamiana reduced susceptibility to L. theobromae, and the silencing of NbPsbQ2 enhanced L. theobromae infection. LtGAPR1 and NbPsbQ2 were confirmed to interact with each other. Transiently, expressed LtGAPR1 activated reactive oxygen species (ROS) production in N. benthamiana leaves. However, in NbPsbQ2-silenced leaves, ROS production was impaired. Overall, our report revealed that LtGAPR1 promotes ROS accumulation by interacting with NbPsbQ2, thereby triggering plant defenses that negatively regulate infection.

The clinical features of papillary thyroid cancer in Hashimoto's thyroiditis patients from an area with a high prevalence of Hashimoto's disease.

BACKGROUND: The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto's thyroiditis (HT) and provide information to aid in the diagnosis of such patients. METHODS: This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients. RESULTS: There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels. CONCLUSION: PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.

Function of Plasmodesmata in the Interaction of Plants with Microbes and Viruses.

Plasmodesmata (PD) are gated plant cell wall channels that allow the trafficking of molecules between cells and play important roles during plant development and in the orchestration of cellular and systemic signaling responses during interactions of plants with the biotic and abiotic environment. To allow gating, PD are equipped with signaling platforms and enzymes that regulate the size exclusion limit (SEL) of the pore. Plant-interacting microbes and viruses target PD with specific effectors to enhance their virulence and are useful probes to study PD functions.

In Vivo Aniline Blue Staining and Semiautomated Quantification of Callose Deposition at Plasmodesmata.

The deposition and turnover of callose (beta-1,3 glucan polymer) in the cell wall surrounding the neck regions of plasmodesmata (PD) controls the cell-to-cell diffusion rate of molecules and, therefore, plays an important role in the regulation of intercellular communication in plants.Here we describe a simple and fast in vivo staining procedure for the imaging and quantification of callose at PD. We also introduce calloseQuant, a plug-in for semiautomated image analysis and non-biased quantification of callose levels at PD using ImageJ.

Salvage surgery for neck residue or recurrence of nasopharyngeal carcinoma: a 10-year experience.

BACKGROUND: To assess the outcome of and determine prognostic factors for neck residue or recurrence of nasopharyngeal carcinoma (NPC) in patients treated with a salvage neck dissection. MATERIALS AND METHODS: Over a 10-year period (from January 1998 through December 2007) in a tertiary hospital, we systematically reviewed the clinical charts of 355 patients with NPC who were diagnosed with neck residue or recurrence of nasopharyngeal carcinoma, after radical definitive radiotherapy with or without chemotherapy. RESULTS: The group with recurrent nodal disease consisted of 285 patients (80.3%), while the group with residual nodal disease included 70 patients (19.7%). There were no patients died of the surgery complications. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were 54.11, 35.01, and 55.59%, respectively, at 3-year, and 26.03, 22.65, and 27.84%, respectively, at 5-year. The local control rate in the neck was 70.92% at 3 years and 60.98% at 5 years. For all the 3 survival outcomes (OS, DFS, and DSS) and the local control rate of disease in the neck, there were significant differences between the "residue group" and "recurrence group." CONCLUSIONS: Radical neck dissection is proven to be safe and effective in the treatment of the neck failure. Our study has demonstrated that it may be possible to choose the selective lymph node dissection for patients of the residue group.

Potential Impact of Global Warming on Virus Propagation in Infected Plants and Agricultural Productivity.

The increasing pace of global warming and climate instability will challenge the management of pests and diseases of cultivated plants. Several reports have shown that increases in environmental temperature can enhance the cell-to-cell and systemic propagation of viruses within their infected hosts. These observations suggest that earlier and longer periods of warmer weather may cause important changes in the interaction between viruses and their host's plants, thus posing risks of new viral diseases and outbreaks in agriculture and the wild. As viruses target plasmodesmata (PD) for cell-to-cell spread, these cell wall pores may play yet unknown roles in the temperature-sensitive regulation of intercellular communication and virus infection. Understanding the temperature-sensitive mechanisms in plant-virus interactions will provide important knowledge for protecting crops against diseases in a warmer climate.

The application of selective neck dissection while preserving the cutaneous branches of cervical plexus in the surgical treatment of differentiated thyroid cancer-experiences from thousands of cases.

Differentiated thyroid cancer (DTC) is associated with the highest propensity for lymph node metastases, given the significant morbidity associated with sacrificing the spinal accessory nerve, surgeons increasingly looked to minimizing functional deficits while maintaining oncologic outcome. We have detailed the technique of a selective neck dissection with more attention to preserving the cervical sensory nerves since 1999 in Fudan University Shanghai Cancer Center. We found that the radical dissection with preservation of the cutaneous branches including the great auricular nerve, the less occipital nerve and the supraclavicular nerve can maximally decrease the complications of paresthesia and dysesthesia postoperatively in the lower neck, the shoulders and the area around the ear in DTC cases when indications were allowed. As long as the principles of cancer surgery are strictly followed, our approach guarantees radical tumor removal and exhibit more functional preservation.

Incidentally simultaneous occurrence of RET/PTC, H4-PTEN and BRAF mutation in papillary thyroid carcinoma.

Because interaction existed between PTEN and RET-RAS-RAF-MAPK pathway, H4-PTEN (a newly identified gene rearrangement), RET/PTC and BRAF mutation were scanned in 125 Chinese patients with papillary thyroid carcinoma (PTC). H4-PTEN were detected in 9.6% of PTC and the frequency of the occurrence of BRAF mutation and/or RET/PTC in H4-PTEN positive tumors was extremely high (75%). On the other hand, age has an important effect on the aberration formation and young age renders more prone to multi-genetic events. A combinational scanning of these involved changes will improve the predictive value of molecular aberrations in the treatment of PTC.

Long-term impact of initial surgical and medical therapy on young patients with papillary thyroid cancer and bilateral cervical metastases.

BACKGROUND: There are few reviews on the clinical features and prognosis of young patients with papillary thyroid cancer and bilateral cervical metastases. We have investigated the long-term impact of initial surgical and medical therapy on such patients. METHODS: A retrospective study was performed on 24 young patients (11 females and 13 males) with papillary thyroid cancer and bilateral cervical lymph node metastases, ranging in age from 11 to 20 years (mean age, 16.6 years), who were treated in our institution from 1 January 1970 to 31 December 1985. RESULTS: All the patients in this group were followed up for 20 years. The survival of the patients at 20 years was 91.7%. The recurrence of local tumor and distant metastases was 20.8% and 12.5%, respectively. Based on analysis of the clinical data, we determined that the completeness of the surgical excision had a significant correlation with tumor recurrence. CONCLUSION: These young patients with papillary thyroid cancer and cervical metastases have a good prognosis after suitable treatment.

[Predictive factors for level VI lymph node metastasis in papillary thyroid microcarcinoma].

OBJECTIVE: To determine the predictive factors for level VI lymph node (LN) metastasis in thyroid papillary microcarcinoma (PTMC). METHODS: From November 2005 to January 2007, 86 patients with PTMC with a lateral cN0 were treated by thyroidectomy and elective level VI LN dissection without comprehensive lateral neck dissection. The data from the cases were analyzed retrospectively to determine the predictive factors for level VI LN metastasis. RESULTS: Forty cases (46.5%) of the patients were found with level VI LN metastasis. Tumor size (> or = 5 mm), thyroid capsular invasion or extracapsular invasion, enlarged level VI LN size (> or = 4 mm) were found significantly related to level VI LN metastasis on univariate analysis (P < 0.05). Tumor size (> or = 5 mm) and thyroid capsular invasion or extracapsular invasion were found to be independent predictive factors for level VI LN metastasis on multivariate analysis (P < 0.05). CONCLUSIONS: Thyroid capsular invasion or extracapsular invasion, tumor size (> or = 5 mm) were significantly associated with level VI LN metastasis in patients with PTMC. Elective neck dissection in level VI should be considered particularly in patients with thyroid capsular invasion or extracapsular invasion and a tumor greater than 5 mm.

[Surgical management of papillary thyroid carcinoma with endotracheal infiltration].

OBJECTIVE: To investigate the diagnosis and treatment of papillary thyroid carcinoma with endotracheal infiltration. METHODS: Clinical data of 12 patients treated from January 1999 to December 2006 were retrospectively analyzed. Six patients received tracheal partial resection-sternocleidomastoid musculoperiosteal flap reconstruction (group A). Six patients received tracheal sleeve resection-end to end anastomosis (group B). RESULTS: Ten patients had the symptoms which indicated the tracheal invasion. Endotracheal focuses were detected in the region from 2 cm to 4 cm under glottis by endoscopy and positive rate of smear biopsy was 33%. Positive rate of CT scan was 92%. Mean diameter of carcinoma focus was 3.8 cm (from 3 cm to 7 cm), and mean number of tracheal ring resected was 4. For group A, even 7 rings were resected, and the longest longitude and latitude was 7 cm and 3 cm, respectively. For group B, the greatest number of rings resected was 4. Incidence rate of perioperative complication and mortality was 58% and 0%, respectively. Mean duration of follow-up was 49 months. One patient died of local recurrence, 1 patient died of lung metastasis. Two patients with tumor recurrence were also alive. For group A, extubation was successful in all patients. CONCLUSIONS: Comprehensive use of diagnostic methods, especially MRI, will give detailed information for operation. Tracheal partial resection-sternocleidomastoid musculoperiosteal flap reconstruction and tracheal sleeve resection-end to end anastomosis are safe and useful methods to reconstruct the defects caused by tracheal operation.

Programmed Death-Ligand 1 Expression in Papillary Thyroid Cancer and Its Correlation with Clinicopathologic Factors and Recurrence.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been reported in several malignancies, but the expression of PD-L1 in papillary thyroid cancer (PTC) has been characterized rarely. The aim of this study was to assess the significance of PD-L1 expression and its associations with clinicopathologic factors and disease outcome in PTC. METHODS: Immunohistochemistry staining was conducted retrospectively to evaluate the expression of PD-L1 in a total of 260 PTC tumors and corresponding non-tumor tissues. The correlations between PD-L1 expressions with clinicopathologic features and recurrence-free survival (RFS) were analyzed. RESULTS: PD-L1 expression was positive in 52.3% (136/260) of PTC tumor tissues, which was significantly higher than in corresponding non-tumor thyroid tissues. In clinicopathologic analyses, this positive staining of PD-L1 was positively linked to multifocality (p = 0.001) and extrathyroidal extension (p = 0.001). In multivariate Cox regression analysis, positive PD-L1 expression in tumor tissue was significantly associated with worse RFS (hazard ratio 2.825 [confidence interval 1.149-6.943], p = 0.024). In subgroup analyses based on clinicopathologic factors, positive PD-L1 staining of tumor tissue was associated with worse RFS in males (p = 0.001), older patients (≥45 years; p = 0.001), and patients with a primary tumor size >4 cm (p = 0.002), multifocal tumors (p = 0.031), extrathyroidal extension (p = 0.012), and lymph node metastasis (p = 0.004). In contrast, positive PD-L1 staining predicted worse RFS in the subgroup of patients without Hashimoto's thyroiditis (p = 0.001) and treated with total thyroidectomy (p = 0.019). CONCLUSIONS: PD-L1 is important in determining aggressiveness of PTC and could predict the prognosis of patients. Therefore, inhibition of PD-L1 is suggested as a potential strategy for the treatment of advanced PTC with high expression of PD-L1.

STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/Snail signaling.

The mammalian peptide hormone stanniocalcin 2 (STC2) plays an oncogenic role in many human cancers. However, the exact function of STC2 in human head and neck squamous cell carcinoma (HNSCC) is unclear. We aimed to examine the function and clinical significance of STC2 in HNSCC. Using in vitro and in vivo assays, we show that overexpression of STC2 suppressed cell apoptosis, promoted cell proliferation, migration, invasion, and cell cycle arrest at the G1/S transition. By contrast, silencing of STC2 inhibited these activities. We further show that STC2 upregulated the phosphorylation of AKT and enhanced HNSCC metastasis via Snail-mediated increase of vimentin and decrease of E-cadherin. These responses were blocked by silencing of STC2/Snail expression or inhibition of pAKT activity. Furthermore, clinical data indicate that high STC2 expression was associated with high levels of pAKT and Snail in tumor samples from HNSCC patients with regional lymph node metastasis (P < 0.01). Thus, we conclude that STC2 controls HNSCC metastasis via the PI3K/AKT/Snail signaling axis and that targeted therapy against STC2 may be a novel strategy to effectively treat patients with metastatic HNSCC.

Prognostic significance and optimal cutoff of age in medullary thyroid cancer.

Age has been found to correlate with the prognosis for medullary thyroid cancer (MTC). This study was conducted to investigate whether age can predict long-term unfavorable prognosis and evaluate its predictive accuracy associated with TNM staging, using data of patients diagnosed with MTC between 2000 and 2010 from Surveillance, Epidemiology and End Results database. The relationship between the patients' age at diagnosis and cancer-specific survival (CSS) was evaluated using multivariate Cox regression analysis. Age stratifications were combined into a nomogram model to predict the CSS of MTC. The X-tile program determined 49 and 69 as optimal age cutoff values for CSS. On multivariate analysis, independent factors for survival were age (50-69 years, HR 2.853, 95% CI 1.631-4.991; ≥70 years, HR 5.804, 95% CI 2.91-11.555), race (white, HR 0.344, 95% CI 0.188-0.630), T (T3/4, HR 3.931, 95% CI 2.093-7.381), N (N1a, HR 3.269, 95% CI 1.386-7.710) and M (M1, HR 3.998, 95% CI 2.419-6.606). The C-index for CSS prediction with TNM, age (cutoff of 45)/sex/race/TNM and age (cutoff of 49 and 69)/sex/race/TNM were 0.832 (95% CI 0.763-0.901), 0.863 (95% CI 0.799-0.928), and 0.876 (95% CI 0.817-0.935), respectively. Subgroup multivariate analyses also showed that age significantly increased the risk for CSS in females, non-Hispanic white patients, and those with stage IV MTC. In conclusion, CSS was independently associated with ages between 49 and 69 years, which might be applied for risk stratification in MTC patients.

[Twenty-four cases of carcinoma in pleomorphic adenoma in the salivary gland].

OBJECTIVE: To study the clinical characteristics, treatment and prognosis 24 cases of carcinoma in pleomorphic adenoma in salivary gland. METHODS: The clinical data of 24 patients with carcinoma in pleomorphic adenoma treated in our hospital from September 1974 to July 1995 were analyzed. RESULTS: The overall 5-year survival rate was 66.7%. The five-year survival rates of patients with carcinoma in pleomorphic adenoma in the major and minor salivary glands were 63.6% and 2/2, respectively. CONCLUSION: Operation is the optimal treatment and extensive resection at the initial operation is suggested. For lumps in the submaxillary gland, preventive neck dissection should be considered. Postoperative radiotherapy can not improve the local-control rate.