Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Identification of differentially-expressed genes of rice in overlapping responses to bacterial infection by Xanthomonas oryzae pv.oryzae and nitrogen deficiency

Bacterial blight of rice caused by Xanthomonas oryzae pv.oryzae（Xoo） is one of high nitrogen（N） responsive diseases.Rice plants became more disease resistant with decreasing N suggesting that the crosstalk between disease resistance and N utilization pathways might exist.However,the co-regulatory components in such crosstalk have not been elucidated.Here,we comparatively analyzed the gene expression profiling of rice under Xoo inoculation,low N treatment,or a combination of both stresses,and identified the differentially-expressed genes（DEGs） in overlapping responses.These DEGs were involved in different biological processes,including innate immunity and nitrogen metabolism.The randomly-selected DEGs expression was validated by quantitative real-time PCR assays.Temporal expression of six genes from different functional categories suggested that N condition was the dominant factor when both stresses were present.These DEGs identified provide novel insights into the coordinated regulatory mechanism in biotic and abiotic stress responses in rice.

Quasi-static and dynamical analyses of a thermoviscoelastic Timoshenko beam using the differential quadrature method

The quasi-static and dynamic responses of a thermoviscoelastic Timoshenko beam subject to thermal loads are analyzed. First, based on the small geometric deformation assumption and Boltzmann constitutive relation, the governing equations for the beam are presented. Second, an extended differential quadrature method(DQM)in the spatial domain and a differential method in the temporal domain are combined to transform the integro-partial-differential governing equations into the ordinary differential equations. Third, the accuracy of the present discrete method is verified by elastic/viscoelastic examples, and the effects of thermal load parameters, material and geometrical parameters on the quasi-static and dynamic responses of the beam are discussed. Numerical results show that the thermal function parameter has a great effect on quasi-static and dynamic responses of the beam. Compared with the thermal relaxation time, the initial vibrational responses of the beam are more sensitive to the mechanical relaxation time of the thermoviscoelastic material.

Assessment of achievements of the Lima Climate Change Conference and perspectives on the future

The Lima call for climate action adopted at the Lima Climate Conference on Climate Change specifies that the principles of the United Nations Framework Convention on Climate Change,including the principle of common but differentiated responsibilities,shall apply to the new climate agreement to be adopted at the Paris Conference on Climate Change in 2015.Decisions on other heavily debated items,including the intended nationally determined contributions,were also made at the Lima Conference.The significant achievements in Lima and the positive momentum have laid a solid foundation for the adoption of a new climate agreement in the Paris Climate Conference.Four measures are proposed for China to meet great challenges in addressing climate change beyond 2020,including early formulation and issuance of a climate change law,establishment of a greenhouse gas emission trading scheme,promotion of advanced climate technology investments,and further international engagement for climate change.

Regulatory Effects of AT1R-TRAF6-MAPKs Signaling on Proliferation of Intermittent Hypoxia-induced Human Umbilical Vein Endothelial Cells

Summary： Endothelial dysfunction induced by intermittent hypoxia （IH） participates in obstructive sleep apnea syndrome （OSAS）-associated cardiovascular disorders. Myeloid differentiation primary response 88 （MyD88） and tumor necrosis factor receptor-associated factor 6 （TRAF6） regulate nu- merous downstream adaptors like mitogen-activated protein kinases （MAPKs） and the subsequent oxidative stress and inflammatory responses. This study aimed to characterize the role of MyD88/TRAF6 in IH-treated cell function and its associated signaling. Human umbilical vein endo- thelial cells （HUVECs） were randomly exposed to IH or normoxia for 0, 2, 4 and 6 h. Western blot- ting was used to detect the expression pattern of target gene proteins [angiotensin 1 receptor （AT1R）, p-ERK1/2, p-p38MAPK, MyD88 and TRAF6], and the relationships among these target genes down-regulated by the corresponding inhibitors were studied. Finally, the influence of these target genes on proliferation of HUVECs was also assessed by EdU analysis. Protein levels of AT1R, TRAF6 and p-ERK1/2 were increased after IH exposure, with a slight rise in MyD88 and a dynamic change in p-p38MAPK. The down-regulation of TRAF6 by siRNA reduced ERK1/2 phosphorylation during IH without any effects on ATIR. Blockade of AT1R with valsartan decreased TRAF6 and p-ERK1/2 protein expression after IH exposure. ERK1/2 inhibition with PD98059 suppressed only AT1R expression. IH promoted HUVECs proliferation, which was significantly suppressed by the in- hibition of TRAF6, AT1R and ERK1/2. The findings demonstrate that TRAF6 regulates the prolifera- tion of HUVECs exposed to short-term IH by modulating cell signaling involving ERK1/2 down- stream of AT1R. Targeting the AT1R-TRAF6-p-ERK1/2 signaling pathway might be helpful in re- storing endothelial function.

Regression Model to Analyze Differential Response to Treatment in Randomized Controlled Clinical Trial

The primary aim of clinical trials is to investigate whether a treatment is effective for a particular disease or condition. Randomized controlled clinical trials are considered to be the gold standard for evaluating the effect of a certain intervention. However, in clinical trials, even after randomization, there are situations where the patients differ substantially with respect to the baseline value of the outcome variable. Many a times the response to interventions depends on the baseline values of the outcome variable. When there are baseline-dependent treatment effects, differences among treatments vary as a function of baseline level. Although variation in outcome associated with baseline value is accounted for in ANCOVA, analysis of individual differences in treatment effect is precluded by the homogeneity of regression assumption. This assumption requires that expected differences in outcome among treatments be constant across all baseline levels. To overcome this difficulty, Weigel and Narvaez [7] proposed a regression model for two treatment groups to analyze individual response to treatments in randomized controlled clinical trials. The authors reviewed the model suggested by Weigel and Narvaez and extended further for three or more treatment groups. The utility of the model was demonstrated with real life data from a randomized controlled clinical trial of bronchial asthma.

Identification and analysis of differentially expressed genes involved in dark-induced photoperiod response and senescence of soybean leaves by suppression subtractive hybridization

A cDNA subtractive library enriched for dark-induced up-regulated ESTs was constructed by suppression subtractive hybridization(SSH) from leaf tissues of soybean cultivar DongNong L13 treated with short-day(8-h light/16-h dark) and long-day(16-h light/8-h dark) conditions.A total of 148 clones were sequenced,representing 76 unique ESTs which corresponded to about 20% of 738 clones from the cDNA library and showed a significant up-regulation of at least three fold verified by dot blot hybridization.The putative functions of ESTs were predicted by Blastn and Blastx.The 43 differentially expressed genes identified by subtractions were classified according to their putative functions generated by Blast analysis.Genetic functional analysis indicated that putative proteins encoded by these genes were related to diverse functions during organism development,which include biological regulation pathways such as transcription,signal transduction and programmed cell death,protein,nucleic acid and carbohydrate macromolecule degradation,the cell wall modification,primary and secondary metabolism and stress response.Two soybean transcription factors enhanced in SD conditions,GAMYB-binding protein and DNA binding protein RAV cDNAs that may be involved in SD soybean photoperiod response,had been isolated using 5'-and 3'-rapid amplification of cDNA ends(RACE)(Genbank Accession numbers DQ112540 and DQ147914).