Stimulating thyroglobulin to TSH ratio predict long-term efficacy of 131I therapy in patients with differentiated thyroid cancer after total thyroidectomy: a retrospective study.

OBJECTIVE: This study utilized the stimulated thyroglobulin (sTg) to thyroid stimulating hormone (TSH) ratio to predict the long-term efficacy of 131I therapy in patients with moderate-to-high-risk differentiated thyroid cancer (DTC). METHODS: This study retrospectively analyzed 960 DTC patients with a median follow-up time of 30 months (6-92 months). The median age was 44 years. All patients underwent total thyroidectomy, lymph node dissection, and at least one 131I therapy. Patients were subjected to a final efficacy evaluation according to American Thyroid Association's 2015 guidelines. Patients were grouped according to their TSH levels before the initial 131I therapy and the final efficacy evaluation, and factors influencing TSH levels and final efficacy were analyzed. Construction of nomograms using independent risk factors affecting long-term outcomes. The cut-offs of sTg and sTg/TSH ratios were calculated for different long-term outcomes. Progression-free survival (PFS) of patients was analyzed by making Kaplan-Meier survival according to the cut-offs of sTg and sTg/TSH ratio. RESULTS: TSH (mU/L) levels were more concentrated at 60-90 in females (71.5%) and 30-60 in males (39.0%), while patients with younger age, more lymph node metastases, shorter time interval between surgery and the first 131I therapy, and lower dose of levothyroxine sodium taken prior to the first 131I therapy would have higher TSH levels (All P < 0.05).Patients who are male, have primary tumor involvement of the strap muscles, lymph node metastasis, distant metastasis, and higher sTg and sTg/TSH are more likely to have poor long-term outcomes (All P < 0.05).The cut-offs of sTg and sTg/TSH for long-term efficacy were 7.515 and 0.095. STg, sTg/TSH, tumor size, lymph node metastasis, and distant metastasis were shown to be independent risk factors for long-term efficacy. The mean PFSs were longer for patients who had sTg/TSH ≤ 0.095 and/or sTg≤7.515 ug/L. CONCLUSIONS: For patients with moderate-to-high-risk DTC, when sTg>7.515 ug/L and/or sTg/TSH > 0.095 before the first 131I therapy, patients are more likely to have a poor long-term efficacy after full 131I therapy. This means that this group of patients may require further surgical treatment or targeted drug therapy after 131I therapy.

Spatial distribution and risk assessment of pyrethroid insecticides in surface waters of East China Sea estuaries.

Pyrethroid insecticides are the most commonly used household insecticides and pose substantial risks to marine aquatic organisms. many studies have detected pyrethroid insecticides in the waters and estuaries of the western United States, but their distributions within western Pacific estuaries have not been reported. Accordingly, we used high-throughput organic analyses combined with high volume solid-phase extraction to comprehensively assess 13 pyrethroid insecticides in East China Sea estuaries and the Huangpu River. The results demonstrated the presence of various ∑13pyrethroid insecticides in East China Sea estuaries (mean and median values of 8.45 ± 5.57 and 7.78 ng L-1, respectively), among which cypermethrin was the primary contaminant. The concentrations of ∑12pyrethroid insecticide detected in the surface waters at the Huangpu River (mean 6.7 ng L-1, outlet 16.4 ng L-1) were higher than those in the Shanghai estuary (4.7 ng L-1), suggesting that runoff from inland areas is a notable source of insecticides. Wetlands reduced the amount of runoff containing pyrethroid insecticides that reached the ocean. Several factors influenced pesticide distributions in East China Sea estuaries, and higher proportions were derived from agricultural sources than from urban sources, with a higher proportion of agricultural sources than urban sources, influenced by anthropogenic use in the region. Permethrin and cypermethrin were the main compounds contributing to the high ecological risk in the estuaries. Consequently, to prevent risks to marine aquatic life, policymakers should aim to reduce insecticide contaminants derived from urban and agricultural sources.

Ocean current redistributed the currently using Organoamine Pesticides in Arctic summer water.

In a comprehensive study on the presence and distribution of Currently Using Organoamine Pesticides (CUOAPs) in the Arctic Ocean, this study collected and analyzed 36 surface seawater samples during the summer of 2021. The study detected 36 CUOAPs, 17 of these compounds at levels exceeding the Method Detection Limits (MDLs). Concentrations of CUOAPs ranged from 0.11 to 2.94 ng/L, exhibiting an average of 1.83 ± 0.83 ng/L. Spatial distribution analysis revealed lower CUOAP concentrations in the central Arctic Ocean, with Cycloate constituting the most abundant component (23.66 %). The investigation identified terrestrial inputs and long-range atmospheric transport as potential sources of CUOAPs in the Arctic Ocean region. The origins of individual CUOAPs appeared to be associated with application procedures and their propensity for co-occurrence at low latitudes. The study also examined the role of ocean currents in the transport and redistribution of CUOAPs in surface seawater across different regions. While ocean currents played a significant role, the influence of sea ice cover on CUOAP distribution was minimal. An ecological risk assessment analysis underscored the need for regional attention to the presence of CUOAPs in the Arctic Ocean.

Spatiotemporal variations, surface inventory, and cross regional impact of current-use organoamine pesticides in Chinese Marginal Seas.

Current-use Organoamine Pesticides (CUOAPs) are a growing concern as emerging pesticide pollutants that were initially discovered on a large scale in Chinese Marginal Seas (CMSs). The highest level was detected in the East China Sea in the late spring and decreased in the following order: East China Sea (early spring) > the South China Sea > the Bohai Sea. The crucial role played by the Yangtze and Yellow rivers as significant terrestrial sources were established. The fluctuations in the land application and riverine input led to variations in the source, distribution, and seasonal patterns of CUOAPs. Terrestrial-exported CUOAPs were transported and redistributed spatially by the surface ocean currents, resulting in significant regional disparities. The results displayed a pronounced terrestrial source signature and a cross-regional impact. By the ocean current transport, CMSs will likely become a secondary source region for the surrounding seas.

Spatial distribution and risk assessment of conazole fungicides in surface seawater of the East China Sea.

Conazole fungicides (CFs), the common-used pesticide in agriculture distributed widely in the environment. This research analyzed the occurrence, potential sources, and risks of eight CFs in the East China Sea surface seawater in the early summer of 2020. The total CF concentration ranged from 0.30 to 6.20 ng/L, with an average value of 1.64 ± 1.24 ng/L. Fenbuconazole, hexaconazole, and triadimenol were the major CFs that comprised >96 % of the total concentration. The Yangtze River was identified as the significant source of CFs from the coastal regions to the off-shore inputs. Ocean current was the first-order factor controlling the content and distribution of CFs in the East China Sea. Although risk assessment revealed CFs posed a low or no substantial risk to ecology and human health, long-term monitoring was also encouraged. This study provided a theoretical foundation for assessing CFs' pollution levels and potential risks in the East China Sea.

Organophosphorus pesticides in southeastern China marginal seas: Land-based export and ocean currents redistribution.

Organophosphorus pesticides (OPPs) have raised an increasing public concern due to their harmful impacts. To explore the occurrence and distribution of OPPs in southeastern China marginal seas (SCMS), a sampling campaign was carried out from East China Sea (ECS) to South China Sea (SCS). A total of 33 OPPs are quantified with the ΣOPPs concentrations ranging from 4.73 to 14.15 ng/L. Higher ΣOPPs concentrations in the surface seawater from the estuaries of Yangtze River, Minjiang River, and Pearl River than those at other sampling sites indicates that riverine emissions are the principal sources of OPPs in SCMS. Different compositions of OPPs in ECS and SCS highlight the different priority of use categories for OPPs in China coastal region. In addition, the vertical diffusion and upwelling ocean currents play critical roles in the redistribution of OPPs in SCMS. For the first time, the ΣOPPs mass inventories in surface seawater of ECS and SCS are estimated at 8.51 and 11.26 t, respectively. Although the current ecological risk of OPPs is at low level in surface seawater of SCMS, the long-term use and bio-accumulative potential point to the necessity for the normalized monitoring of OPPs in China.

Higher adjuvant radioactive iodine therapy dosage helps intermediate-risk papillary thyroid carcinoma patients achieve better therapeutic effect.

Objective: This retrospective study aims to evaluate the therapeutic effect of varying dosages of adjuvant radioactive iodine (RAI) therapy on intermediate-risk papillary thyroid carcinoma (PTC) patients. Methods: This retrospective study involved a total of 427 intermediate-risk PTC patients, out of which 202 received a 3.7GBq dosage of RAI, and 225 received a 5.55GBq dosage. The evaluation involved assessing the therapeutic outcomes, number of treatment cycles, and successful remnant ablation rates in both dose groups, six months post-adjuvant RAI therapy. Univariate and multivariate logistic regression analyses were employed to identify factors linked with excellent response (ER). Following this, prognostic nomograms were constructed to provide a visual representation of the prediction models. Calibration curves, the concordance index (C-index), and the receiver operating characteristic (ROC) curve were employed to evaluate the predictive performance of these nomograms. The Hosmer-Lemeshow test was applied to assess the models' goodness-of-fit. Additionally, the clinical utility of the prognostic nomograms was appraised through decision curve analysis (DCA). Results: The high-dose (HD) group exhibited significantly higher proportions of ER, single treatment cycles, and successful remnant ablation rates (p<0.05). Being male, receiving a 3.7GBq dose, having an N1b stage, an sTg level ≥10ng/ml, or an sTg/TSH ratio ≥0.11 were independent risk factors for Non-ER. Two prognostic nomograms, "sTg Nomogram" and "sTg/TSH Nomogram", were established. The ranking of factors contributing to ER, in descending order, included the sTg or sTg/TSH ratio, N stage, therapy dosage, sex, and soft tissue invasion. The "sTg/TSH Nomogram" demonstrated a higher C-index compared to the "sTg Nomogram". The calibration curves indicated excellent calibration for both nomograms. DCA demonstrated that the net benefit of the "sTg/TSH Nomogram" was higher than that of the "sTg Nomogram". Conclusion: Higher initial RAI therapy doses can improve therapeutic efficacy for intermediate-risk PTC patients. The developed nomograms, particularly the "sTg/TSH Nomogram", could assist clinicians in optimal therapeutic decision-making.

Occurrence, seasonal variations, and eco-risk of currently using organochlorine pesticides in surface seawater of the East China Sea and Western Pacific Ocean.

We studied 19 targets currently using organochlorine pesticides (CUOCPs) from 98 samples in the Western Pacific Ocean and the East China Sea collected in 2019, 2020, and 2021. The samples were analyzed using a novel High-throat/High-volume Solid-Phase Extraction method. Eighteen individual CUOCPs were above the method detection limits. The levels of ∑19CUOCPs ranged from 0.13 to 17.80 ng/L, with an average of 3.13 ± 14.67 ng/L. Dicofol was the main pollutant in the Western Pacific Ocean, while Pyridaben dominated the East China Sea. In the summer, land-source input was the primary source in the Western Pacific Ocean and the East China Sea. Historical residues were the main source in the East China Sea in spring. In the summer, the ecological risk assessment results indicated a relatively low risk to the Western Pacific Ocean and the East China Sea.

Barley GRIK1-SnRK1 kinases subvert a viral virulence protein to upregulate antiviral RNAi and inhibit infection.

Viruses often usurp host machineries for their amplification, but it remains unclear if hosts may subvert virus proteins to regulate viral proliferation. Here, we show that the 17K protein, an important virulence factor conserved in barley yellow dwarf viruses (BYDVs) and related poleroviruses, is phosphorylated by host GRIK1-SnRK1 kinases, with the phosphorylated 17K (P17K) capable of enhancing the abundance of virus-derived small interfering RNAs (vsiRNAs) and thus antiviral RNAi. Furthermore, P17K interacts with barley small RNA-degrading nuclease 1 (HvSDN1) and impedes HvSDN1-catalyzed vsiRNA degradation. Additionally, P17K weakens the HvSDN1-HvAGO1 interaction, thus hindering HvSDN1 from accessing and degrading HvAGO1-carried vsiRNAs. Importantly, transgenic expression of 17K phosphomimetics (17K5D ), or genome editing of SDN1, generates stable resistance to BYDV through elevating vsiRNA abundance. These data validate a novel mechanism that enhances antiviral RNAi through host subversion of a viral virulence protein to inhibit SDN1-catalyzed vsiRNA degradation and suggest new ways for engineering BYDV-resistant crops.

Juvenile hormone promotes paracellular transport of yolk proteins via remodeling zonula adherens at tricellular junctions in the follicular epithelium.

Juvenile hormone (JH) acts as a gonadotrophic hormone stimulating insect vitellogenesis and oogenesis. Paracellular transport of yolk proteins through intercellular channels (patency) in the follicular epithelium is a developmentally regulated and evolutionarily conserved process during vitellogenesis. However, the mechanisms underlying patency opening are poorly understood. Using the migratory locust Locusta migratoria as a model system, we report here that JH-regulated remodeling of zonula adherens (ZA), the belt-like adherens junction maintaining physical linking between follicle cells controlled the opening of patency. JH triggered phosphorylation of Partitioning defective protein 3 (Par3) via a signaling cascade including G protein-coupled receptor (GPCR), small GTPase Cell division cycle 42 (Cdc42) and atypical Protein kinase C (aPKC). Par3 phosphorylation resulted in its disassociation from ß-Catenin, the cytoplasmic partner of ZA core component E-Cadherin. Release of Par3 from the ß-Catenin/E-Cadherin complex caused ZA disassembly at tricellular contacts, consequently leading to patency enlargement. This study provides new insight into how JH stimulates insect vitellogenesis and egg production via inducing the opening of paracellular route for vitellogenin transport crossing the follicular epithelium barrier.

Population genomics of the food-borne pathogen Vibrio fluvialis reveals lineage associated pathogenicity-related genetic elements.

Vibrio fluvialis is a food-borne pathogen with epidemic potential that causes cholera-like acute gastroenteritis and sometimes extraintestinal infections in humans. However, research on its genetic diversity and pathogenicity-related genetic elements based on whole genome sequences is lacking. In this study, we collected and sequenced 130 strains of V. fluvialis from 14 provinces of China, and also determined the susceptibility of 35 of the strains to 30 different antibiotics. Combined with 52 publicly available V. fluvialis genomes, we inferred the population structure and investigated the characteristics of pathogenicity-related factors. The V. fluvialis strains exhibited high levels of homologous recombination and were assigned to two major populations, VflPop1 and VflPop2, according to the different compositions of their gene pools. VflPop2 was subdivided into groups 2.1 and 2.2. Except for VflPop2.2, which consisted only of Asian strains, the strains in VflPop1 and VflPop2.1 were distributed in the Americas, Asia and Europe. Analysis of the pathogenicity potential of V. fluvialis showed that most of the identified virulence-related genes or gene clusters showed high prevalence in V. fluvialis, except for three mobile genetic elements: pBD146, ICEVflInd1 and MGIVflInd1, which were scattered in only a few strains. A total of 21 antimicrobial resistance genes were identified in the genomes of the 182 strains analysed in this study, and 19 (90%) of them were exclusively present in VflPop2. Notably, the tetracycline resistance-related gene tet(35) was present in 150 (95%) of the strains in VflPop2, and in only one (4%) strain in VflPop1, indicating it was population-specific. In total, 91% of the 35 selected strains showed resistance to cefazolin, indicating V. fluvialis has a high resistance rate to cefazolin. Among the 15 genomes that carried the previously reported drug resistance-related plasmid pBD146, 11 (73%) showed resistance to trimethoprim-sulfamethoxazole, which we inferred was related to the presence of the dfr6 gene in the plasmid. On the basis of the population genomics analysis, the genetic diversity, population structure and distribution of pathogenicity-related factors of V. fluvialis were delineated in this study. The results will provide further clues regarding the evolution and pathogenic mechanisms of V. fluvialis, and improve our knowledge for the prevention and control of this pathogen.

Terrigenous export and ocean currents' diffusion of organophosphorus flame retardants along China's adjacent seas.

High demands for but strict regulatory measures on Organophosphorus Flame Retardants (OPFRs) have resulted in mainland China transitioning from the region that imports OPRFs to one that exports these substances. Simultaneously, large quantities of terrigenous OPFRs have been exported to adjacent seas by the major river systems, particularly the Yangtze River. This study examined the presence of ten OPFRs in China's adjacent seas. High levels of OPFRs were observed in seas south of mainland China, with Tris (2-chloroethyl) phosphate (TCEP) and Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) dominant. The terrigenous OPFRs were redistributed by the ocean surface currents, with OPFRs tending to accumulate in regions with lower current speed. The producers of OPFRs are mainly distributed along the Haihe, Yellow, and Yangtze river systems. The application of OPFRs to electric vehicle charging stations, charging connectors, and 5G infrastructure in the Chinese mainland will likely drive rapid growth in OPFR related industry in the future. The diffusion trend map of OPFR indicated that the Bohai Sea and the central northern Yellow Sea are at high risk of ecological damage in the spring. The offshore region of the north of the South China Sea tended to aggregate more OPFRs in summer. Regions of the OPFR aggregation effect were at a higher risk of ecological damage.

Application of Hi-throat/Hi-volume SPE technique in assessing organophosphorus pesticides and their degradation products in surface water from Tai Lake, east China.

Organophosphorus pesticides (OPPs) are among the most commonly used pesticides worldwide. However, these compounds pose a serious threat to aquatic environments. Here, thirty-seven pesticides and eight degradation products were determined in surface water samples from Tai Lake, East China, using a high-volume solid phase extraction technique (Hi-throat/Hi-volume SPE). Surface water was pumped in-situ through a portable sampler, and OPPs in the water retained on the Hi-volume SPE adsorption column, finally extracted for analysis. This technique efficiently reduced the detection limits to below 0.3 ng/L. In total, 40 out of 45 OPP congeners were detected, which far exceeded the amount of OPPs in previous studies. The total concentration of OPPs ranged between 101.4 and 1530 ng/L (median: 378.9 ng/L). Parathion exhibited the highest concentration (median: 112.0 ng/L), followed by paraoxon-methyl (median: 90.3 ng/L), as well as carbophenothion, fenthion, and mevinphos. Agricultural areas were more polluted than residential and industrial regions. However, degradation products persisted in residential and industrial waters. The ecological risks of OPPs in these areas were estimated based on the risk quotient index (RQ). Parathion, fenthion, carbophenothion, and tolclofos-methyl occurred at high-risk levels, and the levels of degradation products were also non-trivial. Our findings thus indicated that OPP degradation products pose a potential threat to natural environments and should therefore be closely monitored.

Genetic diversity and transmission patterns of Burkholderia pseudomallei on Hainan island, China, revealed by a population genomics analysis.

Burkholderia pseudomallei is a Gram-negative soil-dwelling bacillus that causes melioidosis, a frequently fatal infectious disease, in tropical and subtropical regions. Previous studies have identified the overall genetic and evolutionary characteristics of B. pseudomallei on a global scale, including its origin and transmission routes. However, beyond its known hyperendemicity foci in northern Australia and Southeast Asia, the distribution and genetic characteristics of B. pseudomallei in most tropical regions remain poorly understood, including in southern China. Here, we sequenced the genomes of 122 B. pseudomallei strains collected from Hainan, an island in southern China, in 2002-2018, to investigate the population structure, relationships with global strains, local epidemiology, and virulence and antimicrobial-resistance factors. A phylogenetic analysis and hierarchical clustering divided the Hainan strains into nine phylogenic groups (PGs), 80 % of which were concentrated within five major groups (group 1: corresponding to minor sequence types [STs], 12.3 %; group 3: ST46 and ST50, 31.1 %; group 9: ST58, 13.1 %; group 11: ST55, 8.2 %; group 15: mainly ST658, 15.6%). A phylogenetic analysis that included global strains suggested that B. pseudomallei in Hainan originated from Southeast Asian countries, transmitted in multiple historical importation events. We also identified several mutual transmission events between Hainan and Southeast Asian countries in recent years, including three importation events from Thailand and Singapore to Hainan and three exportation events from Hainan to Singapore, Malaysia, and Taiwan island. A statistical analysis of the temporal distribution showed that the Hainan strains of groups 3, 9, and 15 have dominated the disease epidemic locally in the last 5 years. The spatial distribution of the Hainan strains demonstrated that some PGs are distributed in different cities on Hainan island, and by combining phylogenic and geographic distribution information, we detected 21 between-city transmission events, indicating its frequent local transmission. The detection of virulence factor genes showed that 56 % of the Hainan strains in group 1 encode a B. pseudomallei-specific adherence factor, boaB, confirming the specific pathogenic characteristics of the Hainan strains in group 1. An analysis of the antimicrobial-resistance potential of B. pseudomallei showed that various kinds of alterations were identified in clinically relevant antibiotic resistance factors, such as AmrR, PenA and PBP3, etc. Our results clarify the population structure, local epidemiology, and pathogenic characteristics of B. pseudomallei in Hainan, providing further insight into its regional and global transmission networks and improving our knowledge of its global phylogeography.

The BZR1-EDS1 module regulates plant growth-defense coordination.

Plants have developed sophisticated strategies to coordinate growth and immunity, but our understanding of the underlying mechanism remains limited. In this study, we identified a novel molecular module that regulates plant growth and defense in both compatible and incompatible infections. This module consisted of BZR1, a key transcription factor in brassinosteroid (BR) signaling, and EDS1, an essential positive regulator of plant innate immunity. We found that EDS1 interacts with BZR1 and suppresses its transcriptional activities. Consistently, upregulation of EDS1 function by a virulent Pseudomonas syringae strain or salicylic acid treatment inhibited BZR1-regulated expression of BR-responsive genes and BR-promoted growth. Furthermore, we showed that the cytoplasmic fraction of BZR1 positively regulates effector-triggered immunity (ETI) controlled by the TIR-NB-LRR protein RPS4, which is attenuated by BZR1's nuclear translocation. Mechanistically, cytoplasmic BZR1 facilitated AvrRps4-triggered dissociation of EDS1 and RPS4 by binding to EDS1, thus leading to efficient activation of RPS4-controlled ETI. Notably, transgenic expression of a mutant BZR1 that accumulates exclusively in the cytoplasm improved pathogen resistance without compromising plant growth. Collectively, these results shed new light on plant growth-defense coordination and reveal a previously unknown function for the cytoplasmic fraction of BZR1. The BZR1-EDS1 module may be harnessed for the simultaneous improvement of crop productivity and pathogen resistance.

Occurrence, distribution and risk assessment of organophosphate ester flame retardants and plasticizers in surface seawater of the West Pacific.

Twenty-eight samples of surface seawater were collected from the West Pacific Ocean during 2019 using a high-volume solid-phase extraction with high-throughput organic analysis (Hi-throat/Hi-volume SPE) method, and concentrations of 10 organophosphate ester flame retardants and plasticizers (OPEs) were determined. The total OPE concentration in the samples was 3.02-48.4 ng L-1 (mean 25.0 ± 10.5 ng L-1), with tris(2-chloroethyl) phosphate (TCEP) being the largest contributor. Cluster analysis results showed off-shore input from the coast of East and Southeast Asia was an important source of these chemicals. Tri-p-tolyl phosphate (TpTP) should also be considered for long-term monitoring, because of its high detection frequency. Results of a risk assessment indicated low ecological risk to species in the West Pacific Ocean for TPhP and ΣOPEs. Hazard quotients (HQs) were all <1, indicating that the health risk to humans from these chemicals was at acceptable levels.