Association of thyroid autoimmunity with extra-thyroid diseases and the risk of mortality among adults: evidence from the NHANES.

Background: Thyroid autoimmunity is one of the most prevalent autoimmune diseases. However, its association with extra-thyroid diseases and mortality risk in the general population remains uncertain. Our study aims to evaluate the association of thyroid autoimmunity with extra-thyroid disease and the risk of mortality. Methods: A prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) with participants from 2007-2008, 2009-2010, and 2011-2012, tracking their mortality until 2019. Associations between thyroid autoimmunity, which was defined as having positive thyroid peroxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb), and extra-thyroid disease including diabetes, hypertension, cardiovascular disease, chronic lung disease, arthritis, cancer and chronic renal disease and the risk of mortality were investigated. Results: A total of 7431 participants were included in this study. Positive The prevalence of positive TgAb was 7.54%, and positive TPOAb prevalence was 11.48%. TgAb was significantly associated with diabetes (Model 1: OR=1.64, 95% CI:1.08-2.50; Model 2: OR=1.93, 95% CI: 1.21-3.08) and hypertension (Model 1: OR=0.67, 95% CI: 0.49-0.91; Model 2: OR=0.62, 95% CI: 0.44-0.88). TPOAb was associated with a lower prevalence of chronic lung disease (model 1: OR=0.71, 95% CI: 0.54-0.95; model 2: OR=0.71, 95% CI: 0.53-0.95). No associations were observed between TgAb, TPOAb and other extra-thyroid diseases. Neither TgAb nor TPOAb were associated with all-cause mortality or heart disease mortality. Conclusion: TgAb was linked to a higher prevalence of diabetes and a lower prevalence of hypertension, while TPOAb was associated with a decreased prevalence of chronic lung disease. However, neither TgAb nor TPOAb posed a risk for all-cause mortality or heart disease mortality.

Tri-element nanozyme PtCuSe as an ingenious cascade catalytic machine for the amelioration of Parkinson's disease-like symptoms.

Parkinson's disease (PD), as the second most common neurodegenerative disease after Alzheimer's, has become intractable with the increasing aging global population. The exploration of nanomedicine has broadened the opportunities for developing novel neuroprotective therapies. In particular, polymetallic functional nanomaterials have been widely used in the biomedicine field in recent years, exhibiting flexible and diversified functions and controllable properties. In this study, a tri-element nanozyme (PtCuSe nanozyme) has been developed with desirable CAT- and SOD-like activities for the cascade scavenging of reactive oxygen species (ROS). In particular, the nanozyme is suitable for relieving nerve cell damage by removing reactive oxygen species in cells and mitigating the behavioral and pathological symptoms in animal models of Parkinson's disease. Therefore, this ingenious tri-element nanozyme may have potential in the treatment of Parkinson's disease and other neurodegenerative diseases.

Metabolic syndrome and thyroid Cancer: risk, prognosis, and mechanism.

The increasing incidence of thyroid cancer (TC) cannot be fully explained by overdiagnosis. Metabolic syndrome (Met S) is highly prevalent due to the modern lifestyle, which can lead to the development of tumors. This review expounds on the relationship between Met S and TC risk, prognosis and its possible biological mechanism. Met S and its components were associated with an increased risk and aggressiveness of TC, and there were gender differences in most studies. Abnormal metabolism places the body in a state of chronic inflammation for a long time, and thyroid-stimulating hormones may initiate tumorigenesis. Insulin resistance has a central role assisted by adipokines, angiotensin II, and estrogen. Together, these factors contribute to the progression of TC. Therefore, direct predictors of metabolic disorders (e.g., central obesity, insulin resistance and apolipoprotein levels) are expected to become new markers for diagnosis and prognosis. cAMP, insulin-like growth factor axis, angiotensin II, and AMPK-related signaling pathways could provide new targets for TC treatment.

The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study.

Hepatic encephalopathy (HE) is a central nervous system dysfunction syndrome caused by acute and chronic liver failure or various portal systemic shunt disorders. HE arises from metabolic disorder and excludes other known types of encephalopathy. HE is a major cause of death in people with liver disease. Early diagnosis and timely treatment are key to improving HE prognosis. Herein, we established a model of HE and performed metabolomics to identify 50 significantly differential metabolites between the HE group and control group. The main metabolic pathways associated with these differential metabolites were the purine metabolism, pyrimidine metabolism, aminoacyl tRNA biosynthesis, and glucose metabolism. Through proteomics analysis, we identified 226 significantly differential proteins (52 up-regulated and 174 down-regulated). The main (Kyoto Encyclopedia of Genes and Genomes) enrichment pathways were the Staphylococcus aureus infection, vitamin digestion and absorption, and complement and coagulation cascades. Through the conjoint analysis of proteomics and metabolomics, the differentially present proteins and metabolites were found to be involved in vitamin digestion and absorption, and ferroptosis pathways. In HE, malondialdehyde was significantly elevated, but glutathione was significantly diminished, and the redox balance was destroyed, thus leading to changes in proteins' levels associated with the ferroptosis pathway. In conclusion, this study preliminarily explored the molecular and metabolic mechanisms underlying HE.

Injectable agarose hydrogels and doxorubicin-encapsulated iron-gallic acid nanoparticles for chemodynamic-photothermal synergistic therapy against osteosarcoma.

Osteosarcoma is a malignant bone cancer that usually occurs in children and adolescents. Although chemotherapy, radiotherapy and other methods have been used to treat osteosarcoma, these therapeutic regimens fail to cure this disease completely. Herein, doxorubicin-encapsulated iron-gallic acid (FeGA-DOX) nanoparticles (NPs) were fused with agarose hydrogels (AG) for synergistic therapy of osteosarcoma. Under near-infrared laser irradiation, the local temperature of FeGA-DOX NPs was increased. Therefore, tumour cells were killed using photothermal therapy, and AG dissolved to release FeGA-DOX into the cells. Doxorubicin generates hydrogen peroxide, which is then converted to reactive oxygen species (ROS) via FeGA-DOX by the Fenton reaction, inducing tumour cell apoptosis. ROS induced by chemodynamic therapy compensates for the incomplete cure of osteosarcoma cells. The AG-encapsulated NPs could mediate synergistic chemodynamic and photothermal therapy with self-sufficient H2O2, providing a novel therapeutic strategy for osteosarcoma.

High-Quality Development of Science and Technology Finance and Logistics Industry in the Yangtze River Economic Belt: Coupling Analysis Based on Deep Learning Model.

Using the entropy method, the coupling coordination model, and the Tobit model, the coupling coordination degree of the high-quality development of science and technology finance and the logistics industry in the Yangtze River Economic Belt in China from 2009 to 2020 is measured, and its influencing factors are found. The study found that the overall coupling coordination degree of the Yangtze River Economic Belt has shown a rapid upward trend; the development gap of the interprovincial coupling coordination degree has a narrowing trend. Except for Sichuan Province, the average coupling coordination degree decreases from the downstream to the upstream; the mechanism analysis shows that the coupling effect of the two. There are scale effect, innovation effect, talent effect, and structure effect; the analysis of influencing factors shows that innovation effect and talent effect have the most obvious promoting effect on the coupled and coordinated development of the two. In addition, the upgrading of the industrial structure, the effective driving of science and technology, the improvement of the logistics foundation, and the further development of finance also have a positive effect on it. Finally, according to the conclusions, suggestions are put forward from five aspects: insisting on innovation, talent training, risk prevention, policy orientation, and industrial structure upgrading, so as to realize the further coupling of high-quality development of technology finance and logistics industry.

Hypertension Was Associated with Higher Tumor Stages in Papillary Thyroid Cancer: A Large Sample Single-Center Study.

Background: Hypertension (HTN) is known to increase the risk of thyroid cancer. However, few studies have explored the association between HTN and the prognostic factors of papillary thyroid cancer (PTC). Methods: We retrospectively evaluated 2838 PTC patients treated with surgery at our center between January 2017 and September 2020. The association between both HTN and antihypertensive drug use and the clinicopathological features of the PTC patients was analyzed. The odds ratios (ORs) were estimated using both univariate and multivariate logistic regression models, which were adjusted for the patients' age, sex, and thyroid-stimulating hormone level. Results: A total of 2838 patients were enrolled in this study, including 409 patients with HTN. In the multivariate analysis, HTN was associated with larger tumor size [OR = 1.51, 95% confidence interval (CI): 1.10-2.07], lymph node metastasis (OR = 1.43, 95% CI: 1.02-1.99), and higher tumor stages (OR = 1.79, 95% CI: 1.12-2.86). There was no statistical difference between females >40 years of age and any pathological features, while a positive association was observed between older males and larger tumors (OR = 1.87, 95% CI: 1.01-3.45), and lymph node metastasis (OR = 2.01, 95% CI: 1.08-3.73). No statistical difference was found in the effects of taking alone calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers, and their combination on the pathological features of PTC. Conclusion: PTC patients with HTN, particularly males of age >40, tend to have invasive features. Common antihypertension therapy appears to exert no effect on the pathological characteristics of these patients.

Application of Metal-Based Nanozymes in Inflammatory Disease: A Review.

Reactive oxygen species (ROS) are metabolites of normal cells in organisms, and normal levels of ROS in cells are essential for maintaining cell signaling and other intracellular functions. However, excessive inflammation and ischemia-reperfusion can cause an imbalance of tissue redox balance, and oxidative stress occurs in a tissue, resulting in a large amount of ROS, causing direct tissue damage. The production of many diseases is associated with excess ROS, such as stroke, sepsis, Alzheimer's disease, and Parkinson's disease. With the rapid development of nanomedicine, nanomaterials have been widely used to effectively treat various inflammatory diseases due to their superior physical and chemical properties. In this review, we summarize the application of some representative metal-based nanozymes in inflammatory diseases. In addition, we discuss the application of various novel nanomaterials for different therapies and the prospects of using nanoparticles (NPs) as biomedical materials.

Clinical and prognosis value of the number of metastatic lymph nodes in patients with papillary thyroid carcinoma.

OBJECTIVE: It has been reported that papillary thyroid carcinoma (PTC) patients with lymph node metastasis (LNM) are largely associated with adverse outcomes. The present study aimed to assess the correlation between the number of metastatic lymph nodes (NMLNs) and clinical prognosis in patients with PTC. METHODS: We retrospectively reviewed the medical records of patients with PTC who underwent initial thyroid cancer surgery in Renmin Hospital of Wuhan University between 2017 and 2019. A total of 694 patients with PTC and cervical lymph node dissection as well as a total checked number of lymph nodes ≥ 5 were involved in this study. The clinicopathological characteristics of patients were compared according to NMLNs, the number of central cervical lymph nodes (CLNs) and the number of lateral lymph nodes (LLNs). RESULTS: NMLNs > 5, CLNs > 5 and LLNs > 5 were 222 (32.0%), 159 (24.3%) and 70 (10.1%) seen in the analyzed samples, respectively. Young patients, patients with larger tumor diameter, bilaterality, multifocality and gross extrathyroidal extension (ETE) were more inclined to NMLNs > 5, CLNs > 5 and LLNs > 5 (P < 0.05). It was found that the recurrence-free survival among pN1 patients was significantly discrepant between different groups (NMLNs ≤ 5/5: P = 0.001; LLNs ≤ 5/5: P < 0.001). In multivariate logistic regression analysis, patients aged < 55 years (OR = 1.917), primary tumor size > 10 mm (OR = 2.131), bilaterality (OR = 1.889) and tumor gross ETE (OR = 2.759) were independent predictors for high prevalence of total NMLNs > 5 (P < 0.05). Specially, patients aged < 55 years (OR = 2.864), primary tumor size > 10 mm (OR = 2.006), and tumor gross ETE (OR = 2.520) were independent predictors for high prevalence of CLNs > 5 (P < 0.01); Bilaterality (OR = 2.119), CLNs > 5 (OR = 6.733) and tumor gross ETE (OR = 4.737) were independent predictors for high prevalence of LLNs > 5 (P < 0.05). CONCLUSIONS: In conclusion, it is evident that NMLNs is related to the invasive clinicopathological features and adverse outcome of patients with PTC which should be correctly evaluated to provide an appropriate guidance for reasonable treatment and careful follow-up.

The Impacts of Early-life Adversity on Striatal and Hippocampal Memory Functions.

The impacts of early-life adversity (ELA) on cognitive functions including striatal-dependent habit memory and hippocampal-dependent spatial memory were investigated in male mice. The ELA mouse model was generated via an altered cage environment with limited nesting and bedding materials during postnatal days 2-9 (P2-9). The altered cage environment affected the nesting behaviors of dams, creating a stressful condition for their offspring. The ELA mice had biased decision making and poor spatial memory when they grew into young adults (4-month-old). To explore the underlying synaptic basis of these effects, excitatory synapses represented by postsynaptic density protein-95 (PSD-95) were immunolabelled on a series of brain sections and stereologically quantified in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), as well as in area CA1 of the dorsal hippocampus. Increased PSD-95-immunoreactive synapses were observed in DLS but not DMS, whereas selective loss of PSD-95 synapses was detected in the stratum radiatum of area CA1. The spine data supported the selective effects of ELA on PSD-95 synapses. Specifically, both thin and mushroom-type spines were increased in DLS, while loss of thin spines was apparent in CA1 radiatum in ELA mice versus controls. The correlation between PSD-95 synapses and memory performances was further analyzed, and the data suggested that increased small (<0.20 µm3) and large (>0.40 µm3) synapses in DLS might drive ELA mice to make decisions largely relying on habit memory, while loss of small synapses in hippocampal CA1 damage the spatial memory of ELA mice.

Blood-based liquid biopsy: Insights into early detection and clinical management of lung cancer.

Currently, early detection of lung cancer relies on the characterisation of images generated from computed tomography (CT). However, lung tissue biopsy, a highly invasive surgical procedure, is required to confirm CT-derived diagnostic results with very high false-positive rates. Hence, a non-invasive or minimally invasive biomarkers is essential to complement the existing low-dose CT (LDCT) for early detection, improve responses to a certain treatment, predict cancer recurrence, and to evaluate prognosis. In the past decade, liquid biopsies (e.g., blood) have been demonstrated to be highly effective for lung cancer biomarker discovery. In this review, the roles of emerging liquid biopsy-derived biomarkers such as circulating nucleic acids, circulating tumour cells (CTCs), long non-coding RNA (lncRNA), and microRNA (miRNA), as well as exosomes, have been highlighted. The advantages and limitations of these blood-based minimally invasive biomarkers have been discussed. Furthermore, the current progress of the identified biomarkers for clinical management of lung cancer has been summarised. Finally, a potential strategy for the early detection of lung cancer, using a combination of LDCT scans and well-validated biomarkers, has been discussed.

Association between metabolic syndrome and clinicopathological features of papillary thyroid cancer.

BACKGROUND: Metabolic syndrome (MetS) was a risk factor for papillary thyroid cancer (PTC). Whether MetS impacts the aggressiveness of PTC is still unclear. We carried out this study to clarify this issue. METHODS: We evaluated 745 consecutive PTC patients treated with surgery. Patients were divided into three groups based on their number of MetS components: patients without any MetS components, patients with 1-2 MetS components, and patients with 3-5 MetS components. The clinical features and histological aggressiveness of PTC at the time of diagnosis were evaluated. RESULTS: A total of 745 patients were included in this study. And, 145 patients had three or more metabolic components and were diagnosed as MetS. MetS was a risk factor for larger tumors (OR = 2.29, 95% CI: 1.31-4.03), more lymph node metastasis (OR = 1.97, 95% CI: 1.11-3.51), and later clinical stage (OR = 7.92, 95% CI: 1.59-39.34) after correction for age, sex, and thyroid-stimulating hormone (TSH) level and body mass index (BMI). CONCLUSION: In our hospital-based cohort study MetS was associated with the aggressiveness of PTC. This association was still significant after adjusting for age, sex, TSH, and BMI.

More Aggressive Cancer Behaviour in Thyroid Cancer Patients in the Post-COVID-19 Pandemic Era: A Retrospective Study.

PURPOSE: Many thyroid cancer patients have suffered from treatment delays caused by the coronavirus disease 2019 pandemic. Although there have been many reviews, recommendations, or clinical experiences, clinical evidence that evaluates patient disease status is lacking. The aim of our research was to evaluate thyroid cancer behaviour in the post-COVID-19 era. PATIENTS AND METHODS: A retrospective study was conducted and thyroid cancer patient data from February 1, 2017 to September 15, 2020 were pooled for analysis. The demographic, ultrasound and pathological data of the pre- and post-COVID-19 groups were compared. Lymph node metastases, tumour size, extrathyroidal extension, and multifocality were compared year-by-year to evaluate annual changes in patient characteristics. Regression analyses were adopted to reveal cancer behaviour along with the admission date interval and to reveal risk factors for lymph node metastasis. Patient ultrasound data were compared before and after the lockdown to assess tumour progression. The outcomes of delays in treatment ≤180 days were then studied. RESULTS: The post-lockdown patients were more likely to have multiple lesions (31.2% vs 36.5%, p = 0.040), extrathyroidal extension (65.5% vs 72.2%, p = 0.011) and lymph node metastases (37.7% vs 45.0%, p = 0.007), while tumour size remained stable (1.01cm vs.1.02cm, p = 0.758). The lymph node metastasis rate increased by year (p < 0.001). The tumour size correlated negatively with the post-lockdown admission date (p = 0.002). No significant difference in tumour size, multifocality or lymph node metastasis on ultrasound was revealed between the pre- and post-lockdown group. No significant difference in tumour size, multifocality, extrathyroidal extension or lymph node metastasis was revealed among patients with a delayed treatment time ≤180 days. CONCLUSION: Patients with a COVID-19-induced treatment delay had more aggressive cancer behaviour. Rebound medical visits and annually increasing aggressiveness may be potential reasons for this observation, as individual patient tumour did not progress during the delay.

The role of C/EBP homologous protein (CHOP) in regulating macrophage polarization in RAW264.7 cells.

Schistosomiasis is a zoonotic parasitic disease that is endemic in Asia. Macrophages are mainly involved in the inflammatory response of late schistosoma infection. Our previous study found that C/EBP homologous protein (CHOP) expression is significantly increased, and M2 macrophages are activated in schistosome-induced liver fibrosis mice. However, the role of CHOP in the regulation of macrophage polarization remains to be further studied. Western blotting or quantitative PCR revealed that IL-4 increased the expression of arginase-1, macrophage mannose receptor 1, phosphorylation signal transducer and activator of transcription 6 (p-STAT6), Krüppel-like factor 4 (KLF4), CHOP, and IL-13 receptor alpha (IL-13Rα) and induced M2 polarization in RAW264.7 as measured by flow cytometry. Inhibiting STAT6 phosphorylation (AS1517499) reduced the IL-4-induced expression of KLF4, CHOP, and IL-13Rα and also the number of M2 macrophages. The overexpression of CHOP stimulated M2 polarization, but AS1517499 inhibited this effect. CHOP increased the protein expression of KLF4 but did not change the expression of p-STAT6. Soluble egg antigen (SEA) could promote the IL-4-induced protein expression of p-STAT6, CHOP, and KLF4. Overall, the findings show that SEA can promote the activation of M2 macrophages by causing increased CHOP-induced KLF4 levels and activation of STAT6 phosphorylation.

A Co-Expression Network Reveals the Potential Regulatory Mechanism of lncRNAs in Relapsed Hepatocellular Carcinoma.

BACKGROUND: The mechanistic basis for relapsed hepatocellular carcinoma (HCC) remains poorly understood. Recent research has highlighted the important roles of long non-coding RNAs (lncRNAs) in HCC. However, there are only a few studies on the association between lncRNAs and HCC relapse. METHODS: Differentially expressed lncRNAs and mRNAs between a primary HCC group and relapsed HCC group were identified using the edge R package to analyze the GSE101432 dataset. The differentially expressed lncRNAs and mRNAs were used to construct a lncRNA-mRNA co-expression network. Weighted gene co-expression network analysis followed by Gene Ontology (GO) enrichment analyses were conducted on the database. Furthermore, correlation and survival analyses were performed using The Cancer Genome Atlas database, and expression in the clinical samples was verified by qRT-PCR. Thereafter, we inputted the genes from the two groups into the HCC TNM stage and tumor grade database from TCGA. Finally, we performed Kaplan-Meier survival analysis on the lncRNAs related to relapsed HCC. RESULTS: In this study, lncRNAs and mRNAs associated with HCC relapse were identified. Two gene modules were found to be closely linked to this. The GO terms in the yellow and black modules were related to cell proliferation, differentiation, and survival, as well as some transcription-related biological processes. Through qRT-PCR, we found that the expression levels of LINC00941 and LINC00668 in relapsed HCC were higher than those in primary HCC. Further, mRNA levels of LOX, OTX1, MICB, NDUFA4L2, BAIAP2L2, and KCTD17 were changed in relapsed HCC compared to levels in primary HCC. In addition, we verified that these genes could predict the overall survival and recurrence-free survival of HCC. Moreover, we found that LINC00668 and LINC00941 could affect tumor grade and TNM stages. In total, we identified and validated two lncRNAs (LINC00941 and LINC00668) and six mRNAs (LOX, MICB, OTX1, BAIAP2L2, KCTD17, NDUFA4L2) associated with HCC relapse. CONCLUSION: In summary, we identified the key gene modules and central genes associated with relapsed HCC and constructed lncRNA-mRNA networks related to this. These genes are likely to have potential prognostic value for relapsed HCC and might shed new light on novel biomarkers or diagnostic targets for relapsed HCC.

Preclinical evaluation of MRG002, a novel HER2-targeting antibody-drug conjugate with potent antitumor activity against HER2-positive solid tumors.

BACKGROUND: ERBB2 is a proto-oncogene of multiple cancers including breast and gastric cancers with HER2 protein overexpression or gene amplification and has been proven clinically as a valid target for these cancers. HER2-targeting agents such as Herceptin®, Kadcyla® and ENHERTU® have been approved by the FDA for the treatment of breast cancer, but these drugs still face the challenge of acquired resistance and/or severe adverse reactions in clinical use. Therefore, there is significant unmet medical need for developing new agents that are more effective and safer for patients with advanced HER2-positive solid tumors including breast and gastric cancers. METHODS: We report here the making of MRG002, a novel HER2-targeted antibody drug conjugate (ADC), and preclinical characterization including pharmacology, pharmacodynamics and toxicology and discuss its potential as a novel agent for treating patients with HER2-positive solid tumors. RESULTS: MRG002 exhibited similar antigen binding affinity but much reduced antibody-dependent cellular cytotoxicity (ADCC) activity compared to trastuzumab. In addition to potent in vitro cytotoxicity, MRG002 showed tumor regression in both high- and medium-to-low HER2 expressing in vivo xenograft models. Furthermore, MRG002 showed enhanced antitumor activity when used in combination with an anti-PD-1 antibody. Main findings from toxicology studies are related to the payload and are consistent with literature report of other ADCs with monomethyl auristatinE. CONCLUSION: MRG002 has demonstrated a favorable toxicity profile and potent antitumor activities in the breast and gastric PDX models with varying levels of HER2 expression, and/or resistance to trastuzumab or T-DM1. A phase I clinical study of MRG002 in patients with HER2-positive solid tumors is ongoing (CTR20181778).

Citrobacter freundii causing Ginger (Zingiber officinale Rosc.) Rot in Tangshan, China.

Ginger (Zingiber officinale Rosc.) is an important economic crop and its rhizome can be used as seasoning agent and traditional medicine in China. During July 2018 and 2019, decay symptoms occurred in the ginger planting area of Tangshan City, Hebei Province, with incidence rates of 15%～20%. The pathogen infected the rhizomes and leaves. The symptoms included leaves chlorosis and gradually wilting, even the whole plant wilted, the rhizome became soft and presented light brown maceration. In serious cases, the interior of rhizome was completely eroded, gray-white juice overflowing the epidermis, and with foul smell. The rhizome surfaces of ginger plants were disinfected with 1% NaOCl, and colonies were isolated and purified on nutrient agar (NA) solid medium by streaking. Eight isolates were obtained from 15 diseased tissue samples. Further morphological, physiological and biochemical identification of the pure cultured bacteria were carried out. Three strains of bacteria were picked for further analysis. All of the three strains were gram-negative, short rod-shaped，nonmotile bacillus. Colonies were round and milky yellow, smooth raised, and moist after incubation at 28°C for 24h on NA. Physiological and biochemical test results showed that strains were facultatively anaerobic, negative for indole, methyl red, the Voges-Prauskauer test (V-P) and urease; positive for glucose, sucrose, sorbitol, inositol, mannitol, citrate utilization and hydrogen sulfide production; gelatin liquefaction. A typical hypersensitive reaction was induced on 12-week-old tobacco (Nicotiana benthamiana) leaves, which were inoculated by injecting suspensions of the isolated strain (108 CFU/mL) at 25 ℃ after 24h. These characteristics were consistent with Citrobacter freundii (Werkman and Gillen 1932). To further assess the identity of the strains, the genomic DNA was extracted from one bacterium（JXJ4）. The partial 16S rRNA region (Lane 1991) and specific rpoB and gyrB genes (Mollet et al. 1997, Brady et al. 2013) were amplified and sequenced with primers 27F/1492R, CM7/CM31b and UP1f/UP2r, respectively. The obtained 16S, rpoB and gyrB sequences (GenBank accession MN148645, MN158728 and MW199734) of the isolate showed 99.93%, 99.51% and 99.82% identity to the corresponding sequences of C. freundii in GenBank (CP024679.1, CP024677.1 and KM509081.1). Maximum likelihood analysis was performed, and the phylogenetic tree clustered with C. freundii (MEGAX, Bootstrap n=1000). The pathogenicity of the isolates was tested on ginger plants and rhizomes tissue. The bacterial suspensions (108 CFU/mL) of three isolates were injected into the basal stem and rhizomes center of 9 healthy ginger seedlings respectively, and Control groups were treated with sterile water. The inoculated plants were kept in a moist chamber (28°C, 16-h light and 8-h dark period) and ginger rhizomes were placed in the incubator (30°C, 16-h light and 8-h dark period). Seven days after inoculation, the ginger tubers showed symptoms of decay, and 20 to 25 days later, the ginger plant leaves browned and died. The pathogenicity test was repeated 4 times and all controls were healthy. Pathogens were reisolated from symptomatic plants and rhizomes and identified as C. freundii based on the morphological, biochemical and molecular methods described previously, fulfilling Koch's hypothesis. To our knowledge, this is the first report of ginger rot caused by C. freundii in China.

First Report of Colletotrichum cereale Causing Anthracnose on Avena nuda in China.

Naked oats (Avena nuda L.) is rich in protein, fat, vitamin, mineral elements and so on, and is one of the world's recognized cereal crops with the highest nutritional and healthcare value. In July 2019, leaf spot was detected on A. nuda in Zhangbei experimental station of Hebei Agricultural University. The incidence of disease is 10% to 20%. The symptoms were similar to anthracnose disease, the infected leaves had fusiform or nearly fusiform yellowish-brown spots, yellow halo around the spots. Numerous acervuli with black setae diagnostic of fungi in the genus Colletotrichum were present on necrotic lesions. To identify the pathogen, ten symptomatic leaves were collected, and only one disease spot was isolated from each leaf. Small square leaf pieces (3 to 5 mm) were excised from the junction of diseased and healthy tissues with a sterile scalpel and surface disinfested with 75% alcohol for 30s, 0.1% corrosive sublimate for 1 min, rinsed three times in sterile water. Plant tissues were then transferred on potato dextrose agar (PDA), and incubated at 25°C for 7 days. Two fungal isolates were obtained and purified by single-spore isolation method. All fungi have the same morphology and no other fungi were isolated. The aerial mycelium was gray black. The conidia were colorless and transparent, falcate, slightly curved, tapered toward the tips, and produced in acervuli with brown setae. The length and width of 100 conidia were measured and size ranged from 1.86 to 3.84 × 8.62 to 29.81 µm. These morphological characteristics were consistent with the description of Colletotrichum cereale (Crouch et al. 2006). To further assess the identity of the species, the genomic DNA of two fungal isolates (LYM19-4 and LYM19-10) was extracted by a CTAB protocol. The ribosomal DNA internal transcribed spacer (ITS) region as well as, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), and the beta-tubulin 2 (Tub2) partial genes were amplified and sequenced with primers ITS4/5, GDF/GDR, ACT-512F/ACT-783R, and T1/Bt2b, respectively (Carbone et al. 1999; Templeton et al. 1992; O'Donnell et al. 1997; Glass et al. 1995). The sequences of the ITS-rDNA region (MW040121, MW040122), the GAPDH sequences (MW052554, MW052555), the ACT sequences (MW052556, MW052551) and the Tub2 sequences (MW052552, MW052553) of the two single-spore isolates were more than 99% identical to C. cereale isolate CGMCC3.15110 (JX625159, KC843517, KC843534 and JX625186). Maximum likelihood tree based on concatenated sequences of the four genes were constructed using MEGA7. The results showed the strains isolated from A. nuda were closely related to C. cereale, as supported by high bootstrap values. A pathogenicity test of the C. cereale isolates was performed on first unfolding leaves of A. nuda. Koch's postulates were carried out with isolates by spraying a conidial suspension of 106 conidia/mL on leaves of healthy A. nuda. Four replicated pots were inoculated at a time, 10 leaves each pot, while sterile distilled water was used as the control. All treated plants were placed in a moist chamber (25°C, 16-h light and 8-h dark period). Anthracnose symptoms developed on the inoculated plants 7 days post inoculation while all control plants remained healthy. Microscopic examination showed the surface of infected leaves had the same acervuli, setae, and conidia as the original isolate. The pathogenicity test was repeated three times. C. cereale was previously reported as the causal agent of anthracnose on feather reed grass in US (Crouch et al. 2009). To our knowledge, this is the first report of C. cereale as the causal agent of A. nuda anthracnose in China.

Appraisal of radioiodine refractory thyroid cancer: advances and challenges.

The incidence of thyroid cancer ranks top among all endocrine cancers, which has increased worldwide. Some patients suffer from recurrent/residual diseases after primary treatment. The recurrent/residual disease often turns out to be radioiodine refractory and shows poor response to radioiodine therapy. A lot of studies have explored the precise appraisal of radioiodine refractory disease in recent years. The mechanism of iodine uptake and the definition of radioiodine refractory disease have been summarized and discussed. The advances in tumor characteristics, histologies, and mutant conditions have been explored for a more accurate method in the early-stage appraisal. We then offer a review of opinions in the evaluation of refractory disease during follow-up, including Tg doubling time, 18F PET/CT, 131I WBS, and others. The sensitivity and specificity have been compared between different diagnostic methods. Some novel methods may be introduced for more precise appraisal, such as a scoring system and RNA expression profiling. This review aims to provide physicians a broad insight into the appraisal of radioiodine refractory disease and to pave way for future study.