Decabromodiphenyl Ether Exposure Reduces Dabrafenib Sensitivity of Papillary Thyroid Carcinoma Harboring BRAFV600E mutation through the EGFR-CRAF-MAPK Pathway: An In Vitro Study.

Decabromodiphenyl ether (BDE209) has been demonstrated to be associated with thyroid dysfunction and thyroid carcinoma risk as a widely used brominated flame retardants. Although dabrafenib has been confirmed to be a promising therapeutic agent for papillary thyroid carcinoma (PTC) harboring BRAFV600E mutation, the rapid acquired dabrafenib resistance has brought a great challenge to clinical improvement and the underpinning mechanisms remain poorly defined. By treating PTC-derived and normal follicular epithelial cell lines with BDE209, we assessed its impact on the MAPK pathway's activation and evaluated the resultant effects on cell viability and signaling pathways, utilizing methods such as Western blot, IF staining, and RNA-seq bioinformatic analysis. Our findings reveal that BDE209 exacerbates MAPK activation, undermining dabrafenib's inhibitory effects by triggering the EGFR pathway, thereby highlighting BDE209's potential to diminish the pharmacological efficacy of dabrafenib in treating BRAF-mutated PTC. This research underscores the importance of considering environmental factors like BDE209 exposure in the effective management of thyroid carcinoma treatment strategies.

Integrating a Multiple Isotopologue Reaction-Monitoring Technique and LC-MS/MS for Quantitation of Small Molecules: Ten Mycotoxins in Cereals as an Example.

Accurate quantification of mycotoxin in cereals is crucial for ensuring food safety and human health. However, the preparation of traditional multisample external calibration curves (MSCCs) is labor-intensive and error-prone. Here, a multiple isotopologue reaction-monitoring (MIRM)-LC-MS/MS method for accurate quantitation of ten major mycotoxins in cereals was successfully developed and validated, where a novel one-sample multipoint calibration curve (OSCC) strategy is used instead of MSCCs. The OSCC can be established by examining the correlation between the calculated theoretical isotopic abundances and the measured abundance across various MIRM channels. In comparison to the MSCC, the OSCC strategy exhibits outstanding performance including superior selectivity, accuracy (78.4-108.6%), and precision (<12.5%). Furthermore, the proposed OSCC-MIRM-LC-MS/MS method was successfully applied to investigate mycotoxin contamination in cereal samples in China. Considering the advantages of simplified workflows and improved throughput, the OSCC-MIRM-LC-MS/MS methodology holds great promise for accurately quantifying chemical contaminants in foods.

MitoQ protects against carbon tetrachloride-induced hepatocyte ferroptosis and acute liver injury by suppressing mtROS-mediated ACSL4 upregulation.

Ferroptosis has been shown to be involved in carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl4-induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl4-exposed human hepatocytes. Moreover, CCl4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl4-evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl4 exposure. Finally, MitoQ pretreatment alleviated CCl4-induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl4-induced ALI via the mtROS-ACSL4 pathway.

Alexithymia and negative emotions among nursing students: a moderated mediation model.

Nursing students, who comprise a high percentage of China's college students, experience many psychological problems; however, few studies explored the mechanisms underlying these problems. This cross-sectional study explored the relationships and mechanisms of depression, anxiety, stress, and narrative disorders in senior nursing students. Questionnaires were administered to 380 senior nursing students in Hubei Province using the Sociodemographic Questionnaire, Toronto Alexithymia-20 Scale, Perceived Social Support Scale, 10-Item Connor-Davidson Resilience Scale, and Depression-Anxiety-Stress Scale. After controlling for sociodemographic variables, Hayes' PROCESS macros were used to test how psychological resilience moderates the relationships among narrative disorders, negative affect, and perceived social support. Bootstrap confidence intervals tested for indirect effects. Correlation analyses revealed that alexithymia was correlated significantly positively with depression-anxiety-stress (r = 0.57, 0.56, and 0.58, resp.) and significantly negatively with perceived social support (r = 0-0.46). Psychological resilience was correlated significantly negatively with alexithymia (r=-0.39) and depression-anxiety-stress (r=-0.31, -0.30, and-0.32, resp.) but significantly positively with perceived social support(r = 0.50). Perceived social support was correlated significantly negatively with depression-anxiety-stress (r=-0.33, -0.34, and - 0.42 resp.). Stress was correlated significantly positively with anxiety and depression (r = 0.81 and 0.77, resp.). Psychological resilience was a partial mediator between depression and dysphoria (ß=-0.08, p < 0.05). Dysphoria directly predicted anxiety (ß = 0.31) and stress (ß = 0.37); moreover,alexithymia predicted depression not only directly but also through the mediating effect of psychological resilience. Therefore, educators and clinical administrators must promote and recognise negative emotions among nursing students to help ensure the nursing workforce's stability.

Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.

While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAFK601E and BRAFL597R exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.

MYCN amplification is an independent poor prognostic factor in patients with high-risk neuroblastoma (NB). Further exploring the molecular regulatory mechanisms in MYCN-amplified NB will help to develop novel therapy targets. In this study, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) was identified as the differentially expressed gene (DEG) highly expressed in MYCN-amplified NB, and it showed a positive correlation with MYCN and was associated with a poor prognosis of NB patients. Knockdown of MTHFD1 inhibited proliferation and migration, and induced apoptosis of NB cells in vitro. Mouse model experiments validated the tumorigenic effect of MTHFD1 in NB in vivo. In terms of the mechanism, ChIP-qPCR and dual-luciferase reporter assays demonstrated that MTHFD1 was directly activated by MYCN at the transcriptional level. As an important enzyme in the folic acid metabolism pathway, MTHFD1 maintained the NADPH redox homeostasis in MYCN-amplified NB. Knockdown of MTHFD1 reduced cellular NADPH/NADP+ and GSH/GSSG ratios, increased cellular reactive oxygen species (ROS) and triggered the apoptosis of NB cells. Moreover, genetic knockdown of MTHFD1 or application of the anti-folic acid metabolism drug methotrexate (MTX) potentiated the anti-tumor effect of JQ1 both in vitro and in vivo. Taken together, MTHFD1 as an oncogene is a potential therapeutic target for MYCN-amplified NB. The combination of MTX with JQ1 is of important clinical translational significance for the treatment of patients with MYCN-amplified NB.

The effects of NDM-5 on Escherichia coli and the screening of interacting proteins.

Carbapenem-resistant Escherichia coli (E. coli) strains are widely distributed and spreading rapidly, creating significant challenges for clinical therapeutics. NDM-5, a novel mutant of New Delhi Metallo-ß-Lactamase-1 (NDM-1), exhibits high hydrolase activity toward carbapenems. Since the genetic backgrounds of clinically isolated carbapenem-resistant E. coli are heterogeneous, it is difficult to accurately evaluate the impact of blaNDM-5 on antibiotic resistance. Herein, E. coli BL21 was transformed with a plasmid harboring blaNDM-5, and the resultant strain was named BL21 (pET-28a-blaNDM-5). Consistent with the findings of previous studies, the introduction of exogenous blaNDM-5 resulted in markedly greater resistance of E. coli to multiple ß-lactam antibiotics. Compared with BL21 (pET-28a), BL21 (pET-28a-blaNDM-5) exhibited reduced motility but a significant increase in biofilm formation capacity. Furthermore, transcriptome sequencing was conducted to compare the transcriptional differences between BL21 (pET-28a) and BL21 (pET-28a-blaNDM-5). A total of 461 differentially expressed genes were identified, including those related to antibiotic resistance, such as genes associated with the active efflux system (yddA, mcbR and emrY), pili (csgC, csgF and fimD), biofilm formation (csgD, csgB and ecpR) and antioxidant processes (nuoG). Finally, the pGS21a plasmid harboring blaNDM-5 was transformed into E. coli Rosetta2, after which the expression of the NDM-5 protein was induced using isopropyl-ß-D-thiogalactoside (IPTG). Using glutathione-S-transferase (GST) pull-down assays, total proteins from E. coli were scanned to screen out 82 proteins that potentially interacted with NDM-5. Our findings provide new insight into the identified proteins to identify potential antibiotic targets and design novel inhibitors of carbapenem-resistant bacteria.

Whole-exome sequencing reveals causative genetic variants for several overgrowth syndromes in molecularly negative Beckwith-Wiedemann spectrum.

Background Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by (epi)genetic alterations at 11p15. Because approximately 20% of patients test negative via molecular testing of peripheral blood leukocytes, the concept of Beckwith-Wiedemann spectrum (BWSp) was established to encompass a broader cohort with diverse and overlapping phenotypes. The prevalence of other overgrowth syndromes concealed within molecularly negative BWSp remains unexplored.Methods We conducted whole-exome sequencing (WES) on 69 singleton patients exhibiting molecularly negative BWSp. Variants were confirmed by Sanger sequencing or quantitative genomic PCR. We compared BWSp scores and clinical features between groups with classical BWS (cBWS), atypical BWS or isolated lateralised overgrowth (aBWS+ILO) and overgrowth syndromes identified via WES.Results Ten patients, one classified as aBWS and nine as cBWS, showed causative gene variants for Simpson-Golabi-Behmel syndrome (five patients), Sotos syndrome (two), Imagawa-Matsumoto syndrome (one), glycosylphosphatidylinositol biosynthesis defect 11 (one) or 8q duplication/9p deletion (one). BWSp scores did not distinguish between cBWS and other overgrowth syndromes. Birth weight and height in other overgrowth syndromes were significantly larger than in aBWS+ILO and cBWS, with varying intergroup frequencies of clinical features.Conclusion Molecularly negative BWSp encapsulates other syndromes, and considering both WES and clinical features may facilitate accurate diagnosis.

Tigecycline-resistance mechanisms and biological characteristics of drug-resistant Salmonella Typhimurium strains in vitro.

Increased drug resistance of Gram-negative bacteria to tetracycline caused by the unreasonable overuse of tigecycline has attracted extensive attention to reveal potential mechanisms. Here, we identified a tigecycline-resistant strain called TR16, derived from Salmonella Typhimurium ATCC13311 (AT), and examined its biological characteristics. Compared with AT, the TR16 strain showed significantly higher resistance to amoxicillin but lower resistance to gentamicin. Although the growth curves of TR16 and AT were similar, TR16 showed a significantly increased capacity for biofilm formation and a notably decreased motility compared to AT. Furthermore, transcriptome sequencing and reverse transcription-quantitative PCR (RT-qPCR) were implemented to evaluate the genetic difference between AT and TR16. Whole genome sequencing (WGS) analysis was also conducted to identify single nucleotide polymorphism (SNPs) and screened out two genetic mutations (lptD and rpsJ). The acrB gene of TR16 was knocked out through CRISPR/Cas9 system to further elucidate underlying mechanisms of tigecycline resistance in Salmonella Typhimurium. The up-regulation of acrB in TR16 was verified by RNA-seq and RT-qPCR, and the lack of acrB resulted in a 16-fold reduction in tigecycline resistance in TR16. Collectively, these results implied that AcrB efflux pump plays a key role in the tigecycline resistance of Salmonella, shedding light on the potential of AcrB efflux pump as a novel target for the discovery and development of new antibiotics.

The dual HDAC and PI3K inhibitor, CUDC­907, inhibits tumor growth and stem­like properties by suppressing PTX3 in neuroblastoma.

Neuroblastoma (NB) is one of the common solid tumors in childhood and poses a threat to the lives of children. Patients with advanced­stage or recurrent NB have a poor prognosis. CUDC­907, as a novel dual­target inhibitor of histone deacetylase (HDAC) and phosphatidylinositol­3­kinase (PI3K), has been proven to play an antitumor role in several types of tumors. However, the exact role of CUDC­907 in NB remains unclear. In the present study, in vivo and in vitro assays were performed to investigate the anti­NB activity of CUDC­907. Pentraxin 3 (PTX3) small interfering RNA (siRNA) and PTX3 overexpression plasmid were transfected into cells to define the underlying mechanisms of CUDC­907. Tumor tissues and clinical information were collected and immunohistochemistry (IHC) was conducted to analyze the association between the expression of HDAC1, HDAC2, HDAC3 and CD44, and the prognosis of patients with NB. The results indicated that CUDC­907 significantly inhibited the proliferation and migration, and induced the apoptosis of NB cells, downregulating the expression level of MYCN, and suppressing the PI3K/AKT and MAPK/ERK pathways. Furthermore, CUDC­907 suppressed the stem­like properties of NB cells by inhibiting PTX3, a ligand and upstream protein of CD44. IHC revealed that the high expression of HDAC1, 2, 3 and CD44 was associated with a poor prognosis of patients with NB. On the whole, these findings indicate that CUDC­907 may be developed into a possible therapeutic approach for patients with NB.

PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma.

T/NK cell-based immunotherapy has achieved remarkable success in adult cancers but has limited efficacy in pediatric malignancies including high-risk neuroblastoma (NB). Immune defects of NB tumor microenvironment are poorly understood compared with adults. Here, we described the unique characteristics of NB immune contexture and determined the phenotype signatures of PD-L1-expressing CD8+ T and NK cells in NB tumors by systemically analyzing the spatial distribution of T and NK cells and the distinct expression of programmed death 1 (PD-1) and its ligand (PD-L1) in patients with NB. We found that PD-L1-expressing CD8+ T and NK cells in NB tumors were highly activated and functionally competent and associated with better clinical outcomes. Intratumoral NK cells were a favorable prognostic biomarker independent of CD8+ T cells, PD-1/PD-L1 expression, tumor stage, MYCN amplification, and risk classification. NK cells combined with anti-PD-1/PD-L1 antibodies showed potent antitumor activity against both MYCN-amplified and non-amplified NBs in vitro and in vivo, and PD-L1-expressing NK cells associated with improved antitumor efficacy. Collectively, we raise novel insights into the role of PD-L1 expression on CD8+ T-cell and NK-cell activation. We highlight the great potential of intratumoral NK cells in better defining risk stratification, and predicting survival and response to anti-PD-1/PD-L1 therapy in NB. These findings explain why single anti-PD-1/PD-L1 therapy may not be successful in NB, suggesting its combination with NK cell-adoptive cellular therapy as a promising strategy for relapsing/refractory NB. This study provides a potential prospect that patients with PD-L1-expressing NK cells may respond to anti-PD-1/PD-L1 therapy.

Treatment Outcome of Response-Based Radiation Therapy in Children and Adolescents With Central Nervous System Nongerminomatous Germ Cell Tumors: Results of a Prospective Study.

PURPOSE: The optimal dose and range of radiation therapy for central nervous system nongerminomatous germ cell tumors (NGGCTs) have not been uniformly established. Therefore, this study aimed to investigate the effect of individualized radiation therapy, based on the response to induction chemotherapy combined with surgery, on the prognosis of patients with NGGCTs. METHODS AND MATERIALS: Based on the imaging examination and tumor markers after induction chemotherapy and pathologic results of second-look surgery, patients with NGGCT received different radiation therapy strategies, including 30.6 Gy whole ventricular irradiation + tumor-bed boost to 54 Gy, 30.6 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, 36 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, and 36 Gy craniospinal irradiation + 54 Gy tumor-bed boost with 45 Gy to metastatic spinal lesions. RESULTS: A total of 51 patients were enrolled between January 2015 and March 2021, with a median age of 10.3 years. The 3-year event-free survival and overall survival (OS) of the entire cohort were 70.2% ± 6.9% and 77.5% ± 6.0%, respectively. The 3-year OS of patients achieving partial response after induction chemotherapy was higher than that of patients with stable disease (P = .03) or progressive disease (P = .002). The 3-year event-free survival and OS of the 18 patients receiving 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed boost were 88.9% ± 7.4% and 94.4% ± 5.4%, respectively. CONCLUSIONS: The results suggest that an individualized radiation therapy strategy based on response to induction chemotherapy and surgery is a feasible and promising means of achieving reduction in dose and extent of radiation in patients while still providing good response.

The Mechanism of Mori Folium and Eucommiae Cortex against Cyclophosphamide-Induced Immunosuppression Integrating Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations, and Experimental Validation.

It has been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects in the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and EC for the treatment of immunosuppression through network pharmacology, molecular docking, molecular dynamics simulations and animal experiments. As a result, 11 critical components, 9 hub targets, and related signaling pathways in the treatment of immunosuppression were obtained based on network pharmacology. The molecular docking suggested that 11 critical components exhibited great binding affinity to 9 hub targets of immunosuppression. The molecular dynamics simulations results showed that (-)-tabernemontanine-AR, beta-sitosterol-AR and Dehydrodieugenol-HSP90AA1 complexes are stably bound. Additionally, in the animal experiments, the treated group results compared to the control group suggest that MF and EC have a significant effect on the treatment of immunosuppression. Therefore, MF and EC treatment for immunosuppression may take effects in a multi-component, multi-target, and multi-pathway manner. The results herein may provide novel insights into the treatment of immunosuppression in humans.

Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study.

The aim of this phase I study is to evaluate, for the first time, the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies. During the dose escalation phase, patients received a single intravenous infusion of sintilimab at varying doses of 1, 3, and 10 mg/kg. The primary endpoints included the identification of dose-limiting toxicities (DLTs) as well as the evaluation of safety and tolerance. Secondary endpoints focused on assessing objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 29 patients were enrolled, including 10 individuals diagnosed with Hodgkin lymphoma (HL) and 19 patients with various other tumor categories. Notably, diverse pathological types such as thymoma, choroid plexus carcinoma, and NK/T-cell lymphoma were also included in the study cohort. By the safety data cutoff, most adverse events were grade 1 or 2, with grade 3 or higher treatment-related adverse events (TRAE) occurring in 10% of patients. Among the 27 evaluated subjects, four achieved confirmed complete response (CR) while seven patients exhibited confirmed partial response (PR). Additionally, seven patients maintained disease (SD) during the study period. Notably, sintilimab demonstrated remarkable tolerability without DLTs and exhibited promising anti-tumor effects in pediatric HL. Whole-exome sequencing (WES) was conducted in 15 patients to assess the mutational landscape and copy number variation (CNV) status. The completion of this phase I study establishes the foundation for potential combination regimens involving sintilimab in childhood cancer treatment. The trial is registered on ClinicalTrials.gov with the identifier NCT04400851.

The Link between Trace Metal Elements and Glucose Metabolism: Evidence from Zinc, Copper, Iron, and Manganese-Mediated Metabolic Regulation.

Trace metal elements are of vital importance for fundamental biological processes. They function in various metabolic pathways after the long evolution of living organisms. Glucose is considered to be one of the main sources of biological energy that supports biological activities, and its metabolism is tightly regulated by trace metal elements such as iron, zinc, copper, and manganese. However, there is still a lack of understanding of the regulation of glucose metabolism by trace metal elements. In particular, the underlying mechanism of action remains to be elucidated. In this review, we summarize the current concepts and progress linking trace metal elements and glucose metabolism, particularly for the trace metal elements zinc, copper, manganese, and iron.

Reciprocal negative feedback regulation of ATF6α and PTEN promotes prostate cancer progression.

Phosphatase and tensin homolog (PTEN) loss tightly correlates with prostate cancer (PCa) progression and metastasis. Inactivation of PTEN leads to abnormal activation of PI3K/AKT pathway. However, results from clinical trials with AKT inhibitors in PCa have been largely disappointing. Identification of novel regulators of PTEN in PTEN-dysfunctional PCa is urgently needed. Here we demonstrated that the expression level of PTEN is inversely correlated with the signature score of unfolded protein response (UPR) in PCa. Importantly, PTEN suppresses the activity of ATF6α, via interacting to de-phosphorylate ATF6α and consequently inhibiting its nuclear translocation. Conversely, ATF6α promotes the ubiquitination and degradation of PTEN by inducing CHIP expression. Thus, ATF6α and PTEN forms a negative feedback loop during PCa progression. Combination of ATF6α inhibitor with AKT inhibitor suppresses tumor cell proliferation and xenograft growth. Importantly, this study highlighted ATF6α as a therapeutic vulnerability in PTEN dysfunctional PCa.

Treatment outcomes for response-based radiotherapy in children and adolescents with central nervous system germinoma: a prospective study.

PURPOSE: The optimal dose and range of radiotherapy for central nervous system (CNS) germinoma have not yet been established. This study aimed to investigate the effects of individualized radiotherapy on the prognosis of patients with germinoma. METHODS: Based on imaging examination, tumor markers, and pathologic results, patients with germinoma received different radiotherapy strategies, including R1 (24 Gy whole ventricular irradiation + tumor-bed boost to 40 Gy), R2 (24-30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy), R3 (24 Gy craniospinal irradiation + tumor-bed boost to 40 Gy), and R4 (30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy with 45 Gy to spinal metastasis). RESULTS: A total of 77 patients were enrolled in this study between January 2015 and March 2021. The 3-year event-free survival (EFS) and overall survival (OS) of the whole cohort were 94.7% ± 2.6% and 96.0% ± 2.3%, respectively. The 3-year EFS for patients with localized and metastatic disease were 96.6% ± 2.4% and 89.2% ± 7.2%, respectively. The 3-year EFS of patients receiving R1, R2, R3, and R4 radiotherapy were 100%, 94.1% ± 5.7%, 100%, and 86.2% ± 9.1%, respectively. CONCLUSION: Good prognosis was still achieved after reducing dose and extent of radiation for the patients who achieved complete response (CR) after induction chemotherapy or pathological CR after second-look surgery.

Fate of bisphenol A (BPA) in a flooded soil-rice system.

In this study, 14C-tracers were used to investigate the fate of BPA in flooded soil with or without rice plants during a complete growing period. In flooded soil, the dissipation of BPA (half-life 14.8 d) was accompanied by its mineralization (8.4% of the initially applied radioactivity) and the formation of non-extractable residues (NERs) in amounts (79.5%) similar to that formed under oxic conditions. The growth of rice significantly accelerated the dissipation of BPA in flooded soil, resulting in a reduction in both the half-life (5.6 d) and the amount of NERs (35.8%). Two non-polar metabolites were detected both in unplanted and in rice-planted soil. At rice harvest, 57.1% of the radioactivity had accumulated in rice plants, mainly as NERs (54.2%) rather than as extractable radioactivity (2.7%), and mainly in roots (34.5 ± 1.4%), stems (9.4 ± 1.1%), and leaves (8.8 ± 0.6%), with trace amounts in seeds (3.6 ± 0.3%) and seed shells (0.7 ± 0.05%). Our study thus demonstrates that the oxic-anoxic interface stimulates the dissipation of BPA in flooded soil. The link between the releasing of NERs in flooded soil and the uptake of BPA metabolites by rice should be considered in environmental risk assessments of agroecosystems.

Roles and Preliminary Mechanism of Tobacco cis-Abienol in Inducing Tomato Resistance against Bacterial Wilt.

Bacterial wilt negatively impacts the yield and quality of tomatoes. cis-Abienol, a labdane diterpenoid abundantly produced in the trichome secretion of Nicotiana spp., can induce bacterial wilt resistance in plants; however, study on its practical application and acting mechanism is very limited. This study established the application conditions of cis-abienol for inducing tomato bacterial wilt resistance by pot-inoculation experiments and investigated the underlying mechanism by determining the physio-biochemical indexes and transcriptomic changes. The results showed that applying cis-abienol to the roots was the most effective approach for inducing tomato bacterial wilt resistance. The optimal concentration was 60 µg/mL, and 2-3 consecutive applications with 3-6 days intervals were sufficient to induce the bacterial wilt resistance of tomato plants. cis-Abienol could enhance the antioxidant enzyme activity and stimulate the defensive signal transduction in tomato roots, leading to the upregulation of genes involved in the mitogen-activated protein kinase cascade. It also upregulated the expression of JAZ genes and increased the content of jasmonic acid (JA) and salicylic acid (SA), which control the expression of flavonoid biosynthetic genes and the content of phytoalexins in tomato roots. cis-Abienol-induced resistance mainly depends on the JA signalling pathway, and the SA signalling pathway is also involved in this process. This study established the feasibility of applying the plant-derived terpenoid cis-abienol to induce plant bacterial wilt resistance, which is of great value for developing eco-friendly bactericides.

Nonstructural protein VP2 of chicken anemia virus triggers IFN-ß expression via host cGAS.

Chicken anemia virus (CAV) constitutes an important economic threat for the poultry industry. Advancing the understanding of the pathogenic process of CAV infection, we had previously demonstrated that CAV VP1 has the ability to inhibit expression of IFN-ß via cGAS-STING signalling pathway. Here to go further to reveal this regulatory role of viral phosphatase VP2, we have performed protein-protein interaction assays with cGAS adaptors, as well as IFN-ß induction screenings. Contrary to VP1, VP2 of CAV stimulates the expression of IFN-ß, a regulatory effect more closely associated with cGAS (in the context of the cGAS-STING axis) than with STING, TBK1 or IRF7. The results reported here offer new insights about the molecular mechanisms that varied viral proteins act in a timely manner on the host during CAV infection.