Development and validation of a radiosensitivity model to evaluate radiotherapy benefits in pan-cancer.

Radiotherapy, one of the most fundamental cancer treatments, is confronted with the dilemma of treatment failure due to radioresistance. To predict the radiosensitivity and improve tumor treatment efficiency in pan-cancer, we developed a model called Radiation Intrinsic Sensitivity Evaluation (RISE). The RISE model was built using cell line-based mRNA sequencing data from five tumor types with varying radiation sensitivity. Through four cell-derived datasets, two public tissue-derived cohorts, and one local cohort of 42 nasopharyngeal carcinoma patients, we demonstrated that RISE could effectively predict the level of radiation sensitivity (area under the ROC curve [AUC] from 0.666 to 1 across different datasets). After the verification by the colony formation assay and flow cytometric analysis of apoptosis, our four well-established radioresistant cell models successfully proved higher RISE values in radioresistant cells by RT-qPCR experiments. We also explored the prognostic value of RISE in five independent TCGA cohorts consisting of 1137 patients who received radiation therapy and found that RISE was an independent adverse prognostic factor (pooled multivariate Cox regression hazard ratio [HR]: 1.84, 95% CI 1.39-2.42; p < 0.01). RISE showed a promising ability to evaluate the radiotherapy benefit while predicting the prognosis of cancer patients, enabling clinicians to make individualized radiotherapy strategies in the future and improve the success rate of radiotherapy.

Receptor-like kinases OsRLK902-1 and OsRLK902-2 form immune complexes with OsRLCK185 to regulate rice blast resistance.

Receptor-like kinases (RLKs) are major regulators of the plant immune response and play important roles in the perception and transmission of immune signals. RECEPTOR LIKE KINASE 902 (RLK902) is at the key node in leucine-rich repeat receptor-like kinase interaction networks and positively regulates resistance to the bacterial pathogen Pseudomonas syringae in Arabidopsis. However, the function of RLK902 in fungal disease resistance remains obscure. In this study, we found that the expression levels of OsRLK902-1 and OsRLK902-2, encoding two orthologues of RLK902 in rice, were induced by Magnaporthe oryzae, chitin, and flg22 treatment. osrlk902-1 and osrlk902-2 knockout mutants displayed enhanced susceptibility to M. oryzae. Interestingly, the osrlk902-1 rlk902-2 double mutant exhibited similar disease susceptibility, hydrogen peroxide production, and callose deposition to the two single mutants. Further investigation showed that OsRLK902-1 interacts with and stabilizes OsRLK902-2. The two OsRLKs form a complex with OsRLCK185, a key regulator in chitin-triggered immunity, and stabilize it. Taken together, our data demonstrate that OsRLK902-1 and OsRLK902-2, as well as OsRLCK185 function together in regulating disease resistance to M. oryzae in rice.

Comparison of Efficacy of ERCP+LC and LC+LCBDE on Cholecysto-Choledocholithiasis and Analysis of Risk Factors for Recurrence of Choledocholithiasis.

Objective: Laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct exploration (LCBDE) and endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic sphincterotomy (EST) combined with LC are the two primary treatment modalities for common bile duct stones (CCL) at present. The aim of this study is to compare the efficacy and safety of the two surgical approaches in treating CCL and analyze the risk factors for the recurrence of common bile duct stones. Methods: The clinical data of 148 CCL patients treated in the hospital from March 2014 to March 2016 were retrospectively analyzed. ERCP+LC was performed for 74 patients (ERCP+LC group), while the remaining 74 patients underwent LC+LCBDE (LC+LCBDE group). The success rate of lithotomy, operation time, total hospital stay time, postoperative hospital stay time, clinical symptoms, incidence rate of complications, and hospitalization expenses were compared between the two groups. The patients were followed up, the recurrence of choledocholithiasis was recorded, and the risk factors for recurrence were analyzed. Results: The success rate of lithotomy was 97.3% in the LC+LCBDE group and 94.6% in the ERCP+LC group. In the ERCP+LC group and LC+LCBDE group, the average operation time was (125.7±20.3) min and (106.5±25.4) min, the postoperative anal ventilation time was (20.8±3.5) d and (18.7±3.7) d, and the postoperative hospital stay time was (9.3±3.1) d and (7.7±3.3) d, respectively. It can be seen that the above three indexes were all significantly shorter in the LC+LCBDE group than those in ERCP+LC group (P < .001, P < .001, P = .003). The hospitalization expenses in the LC+LCBDE group [(19±1) thousand yuan] were obviously lower than those in the ERCP+LC group [(26±2) thousand yuan] (P < .001). The postoperative symptoms included fever, vomiting, abdominal pain and abdominal distension. The incidence rate of abdominal pain in the LC+LCBDE group was far higher than that in the ERCP+LC group (P = .025), and that of the remaining symptoms had no statistically significant difference between the two groups (P > .05). The postoperative complications mainly included incision infection, bile duct bleeding, biliary fistula, abdominal infection, bile duct pneumatosis, cholangitis and acute pancreatitis. Hyperamylasemia occurred in 8 cases after operation in the ERCP+LC group, greatly more than that in the LC+LCBDE group (1 case) (P = .016), while the incidence of other complications had no statistically significant difference between the two groups (P > .05). The patients were followed up for 3-5 years, and it was found that the recurrence rate of choledocholithiasis was 17.6% and 13.5%, and the mean postoperative recurrence time was 13.7 months and 13.9 months, respectively, in ERCP+LC group and LC+LCBDE group. The results of multivariable logistic regression analysis revealed that the level of cholesterol >572 mm/L (OR=5.108, 95%CI: 1.263-11.472, P = .038), choledochectasia (OR=2.165, 95%CI: 1.019-8.418, P = .034) and parapapillary diverticulum (OR=6.761, 95%CI: 1.334-15.613, P = .039) were independent risk factors for postoperative recurrence of choledocholithiasis. Conclusions: In our study, we found that ERCP+LC and LC+LCBDE have definite efficacy in the treatment of CCL. Patients treated with LC+LCBDE need short hospital stay time and low treatment expenses and have relatively few long-term complications.

OsExo70B1 Positively Regulates Disease Resistance to Magnaporthe oryzae in Rice.

The exocyst, an evolutionarily conserved octameric protein complex, mediates tethering of vesicles to the plasma membrane in the early stage of exocytosis. Arabidopsis Exo70, a subunit of the exocyst complex, has been found to be involved in plant immunity. Here, we characterize the function of OsExo70B1 in rice. OsExo70B1 mainly expresses in leaf and shoot and its expression is induced by pathogen-associated molecular patterns (PAMPs) and rice blast fungus Magnaporthe oryzae (M. oryzae). Knocking out OsExo70B1 results in significantly decreased resistance and defense responses to M. oryzae compared to the wild type, including more disease lesions and enhanced fungal growth, downregulated expression of pathogenesis-related (PR) genes, and decreased reactive oxygen species accumulation. In contrast, the exo70B1 mutant does not show any defects in growth and development. Furthermore, OsExo70B1 can interact with the receptor-like kinase OsCERK1, an essential component for chitin reception in rice. Taken together, our data demonstrate that OsExo70B1 functions as an important regulator in rice immunity.

Quadrangular prism: a unique self-assembly from amphiphilic hyperbranched PMA-b-PAA.

The novel hyperbranched poly(methyl acrylate)-block-poly(acrylic acid)s (HBPMA-b-PAAs) are successfully synthesized via single-electron transfer-living radical polymerization (SET-LRP), followed with hydrolysis reaction. The copolymer solution could spontaneously form unimolecular micelles composed of the hydrophobic core (PMA) and the hydrophilic shell (PAA) in water. Results show that the size of spherical particles increases from 8.18 to 19.18 nm with increased pH from 3.0 to 12.0. Most interestingly, the unique regular quadrangular prisms with the large microstructure (5.70 µm in length, and 0.47 µm in width) are observed by the self-assembly of unimolecular micelles when pH value is below 2. Such self-assembly behavior of HBPMA-b-PAA in solution is significantly influenced by the pH cycle times and concentration, which show that increased polymer concentration favors aggregate growth.

Plant litter as a heavy metal migration strategy following application of sewage sludge to subtropical forest soils.

The environmental risks of migration of heavy metals (HMs) following applications of sewage sludge (SS) to forest soils are garnering increased attention. Plant litter at the forest floor may modify HM migration pathways through impacts on soil aggregates and water/soil erosion; however, HM migration responses to plant litter are poorly understood. The aim of this study was to determine the effects of plant litter cover on HMs migration, and water and soil erosion following the application of SS to subtropical forest soils. Effects of addition of SS along and SS plus plant litter at 0.75 or 1.5 kg m-2 on the migration of cadmium, chromium, copper, nickel, lead, and zinc in surface runoff, soil interflow, and sediments were quantified across nine simulated rainfall events in a laboratory experiment and following natural intense rain events in a field experiment. Addition of SS elevated HM concentrations in surface runoff by 38.7 to 98.5 %, in soil interflow by 48.3 to 312.5 %, and in sediment by 28.5 to 149.4 %, and increased the production of sediment aggregates <0.05 mm that led to greater cumulative migrations of HMs in surface runoff and sediment; sediment accounted for 89.5 % of HM migrations. Addition of plant litter reduced cumulative migration of HMs by 87.1-97.27 %; however, the higher rate of plant litter led to a decrease in surface runoff and sediment yield, and an increase in soil interflow. Addition of plant litter shifted the main pathway of HM migration from sediment to surface runoff and soil interflow. The potential ecological HM risk index was "low" for each treatment. We found consistency in HM concentrations and migrations via surface runoff between the field and laboratory experiments. Overall, the addition of plant litter with SS mitigated soil erosion and reduced total migration of HMs, resulting in a 88.7-97.3 % decrease in the ecological risk index of the six HMs. We conclude that the addition of plant litter may provide a management strategy for the mitigation of HM risks to environmental safety for the disposal of SS in subtropical forest systems.

Effects of woodland slope on heavy metal migration via surface runoff, interflow, and sediments in sewage sludge application.

Sewage sludge (SS) application to forest plantation soils as a fertilizer and/or soil amendment is increasingly adopted in plantation forest management. However, the potential risks of SS-derived heavy metals (HMs) remain a concern. Many factors, including woodland slope may affect the risks, but the understanding of this issue is limited. This research evaluated the HMs migration via surface runoff, interflow, and sediments when SS was applied in woodlands of varying slopes. We conducted indoor rainfall simulations and natural rainfall experiments to clarify the effect of slope on the migration of HMs via runoff (including surface and interflow) and sediments. In the simulated rainfall experiment, HMs lost via sediments increased by 9.79-27.28% when the slope increased from 5° to 25°. However, in the natural rainfall experiment, when the slope of forested land increased from 7° to 23°, HMs lost via surface runoff increased by 2.38% to 6.13%. These results indciate that the surface runoff water on a high slope (25°) posed high water quality pollution risks. The migration of HMs via surface runoff water or interflow increased as the steepness of the slope increased. The total migration of Cu, Zn, Pb, Ni, Cr and Cd via sediment greatly exceeded that via surface runoff and interflow. Particles ≤ 0.05 mm contributed the most to the ecological risks posed by sediments. Cd was the main source of potential ecological risks in sediments under both experimental conditions.

Contrasting terpene emissions from canopy and understory vegetation in response to increases in nitrogen deposition and seasonal changes in precipitation.

Given global change and shifts in climate are expected to increase BVOC emissions, the quantification of links between environmental conditions, plant physiology, and terpene emission dynamics is required to improve model predictions of ecosystem responses to increasing nitrogen deposition and changes in precipitation regimes. Here, we conducted a two-factor field experiment in sub-tropical forest plots to determine effects of N addition (N), precipitation change (PC), and NP (N and PC combined treatment) on wet and dry season terpene emissions and leaf photosynthetic parameters from canopy and understory species. Changes of ß-ocimene and sabinene under PC and NP in the wet season (0.4-5.6-fold change) were the largest contributor to changes in total terpene emissions. In the dry season, the standardized total terpene emission rate was enhanced by 144.9% under N addition and 185.7% under PC for the understory species, while the total terpene emission rate was lower under NP than N addition and PC, indicating that N addition tended to moderate increases in PC-induced understory total terpene emissions. In the wet season, the total terpene emission rate under N and PC was close to ambient conditions for the canopy species, while the total terpene emission rate was enhanced by 54.6% under NP, indicating that N and PC combined treatment had an additive effect on canopy total terpene emissions. Total terpene emission rates increased with rates of net leaf photosynthesis (Pn) and transpiration (Tr) and there was a decoupling between terpene emission rates and Pn under NP, indicating that complex effects between PC and N decreased the regularity of single-factor effects. We recommend that N and PC interaction effects are included in models for the prediction of terpene emissions, particularly from canopy vegetation during the wet season as a major source of forest ecosystem terpene emissions.

B Cell Receptor Signaling Pathway Mutation as Prognosis Predictor of Immune Checkpoint Inhibitors in Lung Adenocarcinoma by Bioinformatic Analysis.

Purpose: The advent of immune checkpoint inhibitors (ICIs) is a revolutionary breakthrough. However, without the selection of a specific target population, the response rate of ICI therapy in lung adenocarcinoma (LUAD) is low, so a clinical challenge has arisen in effectively using biomarkers to determine which patients can benefit from ICI therapy. Methods: In this study, patients were divided according to whether or not nonsynonymous mutations were present in the BCR signaling pathway, and univariate and multivariate Cox regression models were established based on a LUAD cohort treated with ICIs (Miao-LUAD). Then the relationship between the mutation status of the BCR signaling pathway and the prognosis of immunotherapy was examined. Finally, data from The Cancer Genome Atlas (TCGA) LUAD cohort, the Rizvi-LUAD, the Samstein-LUAD, and the Zhujiang Hospital of Southern Medical University LUAD (Local-LUAD) cohort were combined, and the mutation panorama, immunogenicity, tumor microenvironment (TME) and pathway enrichment analysis between the BCR signaling pathway mutant group (BCR signaling MUT) and the BCR signaling pathway wild group (BCR signaling WT) were comprehensively compared. Results: It was found that, compared with the BCR signaling WT, the BCR signaling MUT had a significantly improved progression-free survival (PFS) rate and overall survival (OS) rate, higher immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations), and anti-tumor immune microenvironment. Conclusion: These results revealed that the mutation state of the BCR signaling pathway has potential as a biomarker to predict the efficacy of ICIs in LUAD.

Silicon Amendment Reduces Soil Cd Availability and Cd Uptake of Two Pennisetum Species.

Silicon (Si) plays important roles in alleviating heavy metal stress, but the migrating effects and mechanisms, especially for Pennisetum, are not well studied. In this study, Pennisetum glaucum and Pennisetum glaucum × P. purpureum were used to explore the impacts of Si application on alleviating cadmium (Cd) toxicity and its possible mechanism. Treatments consist of four levels of Cd (0, 10, 50, and 100 mg·kg-1) with or without 2.0 mM Si amendments. Under Cd stress, Si application significantly increased plant biomass and Si content, reduced Cd content, and decreased the enrichment factor in shoots and roots. Si treatment also increased soil pH and soil residual Cd, while reducing available/oxidizable/reducible Cd content in soil at 50 and 100 mg·kg-1 Cd levels, thereby leading to a reduction of the soil's available Cd. These findings indicate that Si application is effective in alleviating Cd phytotoxicity of Pennisetum, mainly through reducing plant Cd uptake and increasing soil pH and Cd immobilization, thereby reducing Cd bioavailability.

Preparation and Properties of Branched Polystyrene through Radical Suspension Polymerization.

Radical solvent-free suspension polymerization of styrene with 3-mercapto hexyl-methacrylate (MHM) as the branching monomer has been carried out using 2,2'-azobisisobutyronitrile (AIBN) as the initiator to prepare branched polymer beads of high purity. The molecular weight and branching structure of the polymers have been characterized by triple detection size exclusion chromatography (TD-SEC), proton nuclear magnetic resonance spectroscopy (¹H-NMR), and Fourier transform infrared spectroscopy (FTIR). The glass transition temperature and rheological properties have been measured by using differential scanning calorimetry (DSC) and rotational rheometry. At mole ratios of MHM to AIBN less than 1.0, gelation was successfully avoided and branched polystyrene beads were prepared in the absence of any solvent. Branched polystyrene has a relatively higher molecular weight and narrower polydispersity (Mw.MALLS = 1,036,000 g·mol-1, Mw/Mn = 7.76) than those obtained in solution polymerization. Compared with their linear analogues, lower glass transition temperature and decreased chain entanglement were observed in the presently obtained branched polystyrene because of the effects of branching.