The function and regulation of PD-L1 in immunotherapy

PD-L1, also known as B7-H1, is a type I transmembrane protein, which is expressed in different kinds of tumor cells. It is correlated with poor clinical outcome of patients with various types of tumors. PD-L1 can regulate tumor microenvironment or tumor related immune response through suppressing T cell or NK cell mediated immune response. PD-L1 expression is regulated by various cytokines, such as LPS, GM-CSF, IL-4, TGF-β, TNF-α. PD-1 and PD-L1 are the members of B7 and CD28 superfamily, respectively. The B7/CD28 interaction plays a central role in immune tolerance. PD-L1 can bind to PD-1, which leads to the suppression of lymphocyte activation and apoptosis of lymphocytes. Anti-PD-L1 therapy is one of the immunotherapies to treat cancer (especially solid tumor). PD-L1 expression may be associated with efficacy of anti PD-1/PD-L1 therapy. In this review, we will focus on the regulation mechanism of PD-L1 expression, and describe the role of PD-1/PD-L1 binding on the anti-PD-1/PD-L1 therapy

Two-parameter estimation with three-mode NOON state in a symmetric three-well

We propose a theoretical scheme to realize two-parameter estimation via a Bose-Einstein condensates confined in a symmetric triple-well. The three-mode NOON state is prepared adiabatically as the initial state. Two phase differences between the wells are two parameters to be estimated. With the help of classical and quantum Fisher information, we study the sensitivity of the triple-well on estimating two phase parameters simultaneously. The result shows that the precision of simultaneous estimation of two parameters in a triple-well system can reach the Heisenberg scaling

Evaluation of anti-smoking television advertising on tobacco control among urban community population in Chongqing, China

Background China is the largest producer and consumer of tobacco in the world. Considering the constantly growing urban proportion, persuasive tobacco control measures are important in urban communities. Television, as one of the most pervasive mass media, can be used for this purpose. Methods The anti-smoking advertisement was carried out in five different time slots per day from 15 May to 15 June in 2011 across 12 channels of Chongqing TV. A cross-sectional study was conducted in the main municipal areas of Chongqing. A questionnaire was administered in late June to 1,342 native residents aged 18–45, who were selected via street intercept survey. Results Respondents who recognized the advertisement (32.77 %) were more likely to know or believe that smoking cigarettes caused impotence than those who did not recognize the advertisement (26.11 %). According to 25.5 % of smokers, the anti-smoking TV advertising made them consider quitting smoking. However, females (51.7 %) were less likely to be affected by the advertisement to stop and think about quitting smoking compared to males (65.6 %) (OR = 0.517, 95 % CI [0.281–0.950]). In addition, respondents aged 26–35 years (67.4 %) were more likely to try to persuade others to quit smoking than those aged 18–25 years (36.3 %) (OR = 0.457, 95 % CI [0.215–0.974]). Furthermore, non-smokers (87.4 %) were more likely to find the advertisement relevant than smokers (74.8 %) (OR = 2.34, 95 % CI [1.19–4.61]). Conclusions This study showed that this advertisement did not show significant differences on smoking-related knowledge and attitude between non-smokers who had seen the ad and those who had not. Thus, this form may not be the right tool to facilitate change in non-smokers. The ad should instead be focused on the smoking population. Gender, smoking status, and age influenced the effect of anti-smoking TV advertising on the general population in China

Regulation of IFN-γ-mediated PD-L1 expression by MYC in colorectal cancer with wild-type KRAS and TP53 and its clinical implications

Introduction: In the tumor microenvironment, interferon gamma (IFN-γ) secreted by tumor infiltrating lymphocytes can upregulate programmed cell death 1 ligand 1 (PD-L1) expression in many cancers. The present study evaluated the expression of PD-L1 in selected colorectal cancer cell lines with IFN-γ treatment and explored the correlation between programmed cell death 1 ligand 1 expression and KRAS/TP53 mutation status.Methods: The selected colorectal cancer cell lines had known KRAS mutations or TP53 mutations. TCGA data analysis were used to investigate the correlation between overall survival of patient with anti-PD-1/PD-L1 immunotherapy and KRAS/TP53 mutation status. Besides, the correlation between PD-L1 expression and KRAS/TP53 mutation status were also investigated by using TCGA data analysis. In vitro experiments were used to explore the mechanism underlying KRAS- and TP53-related PD-L1 expression.Results: Firstly, TCGA data analysis for gene expression and overall survival and an in vitro study revealed that the wild-type KRAS/TP53 cell lines exhibited hyperresponsiveness to interferon gamma exposure and correlated with better survival in patients receiving anti-PD-1/PD-L1 treatment. Secondly, experimental data revealed that interferon gamma induced the upregulation of programmed cell death 1 ligand 1 mainly through regulating MYC in wild-type KRAS and TP53 colorectal cancers.Discussion: Our findings revealed that the response to anti-PD-1/PD-L1 cancer immunotherapy frequently happened in wild-type KRAS and TP53 colorectal cancers, which were also found to show higher programmed cell death 1 ligand 1 expression. Our results indicate that the wild-type KRAS/TP53 colorectal cancer cell lines may respond better to interferon gamma treatment, which causes increased programmed cell death 1 ligand 1 expression and may be a mechanism underlying the better responses to anti-PD-1/PD-L1 therapies in wild-type KRAS and wild-type TP53 colorectal cancer. Furthermore, the experimental results suggest that interferon gamma regulated programmed cell death 1 ligand 1 expression through the regulation of MYC, which may further affect the response to PD-1/PD-L1 cancer immunotherapy. These results suggest a novel potential treatment strategy for enhancing the efficacy of PD-1/PD-L1 blockade immunotherapy in most colorectal cancer patients

Increased growing temperature reduces content of polyunsaturated fatty acids in four oilseed crops

Environmental temperature directly influences the lipid profile produced by oilseeds. If growing temperatures increase, as is predicted by current models, the precise profile of lipids produced are likely to change. This paper develops models to predict lipid profiles as a function of growing temperature. Data relating to lipid profiles of soybean (Glycine max), spring canola (Brassica napus), spring camelina (Camelina sativa), and sunflower (Helianthus annuus) were gathered from the literature and evaluated to examine the influence of temperature on relative production of oleic, linoleic, and linolenic acid. For each crop, a set of linear regressions was used to correlate temperature during the grain fill, defined as 30 days before harvest, with the molar percentages of oleic, linoleic, and linolenic acid present. An increase in temperature from 10 to 40°C resulted in an increase in the production of oleic acid and a decrease in the production of linoleic and linolenic acid in soybeans, canola, and sunflowers. Over the range of data available, the lipid profile of camelina was temperature insensitive. To test the validity of the correlations, the four crops were grown in a field study in Manhattan, Kansas simultaneously, in the same environment, in 2011. The correlations accurately predicted the field data for soybean, canola, and camelina but not for sunflower. The correlation for sunflower under-predicted the molar amount of oleic acid and over-predicted the molar amount of linoleic acid. This study indicates increasing growing temperatures from 10 to 40°C will result in more monounsaturated oils and less polyunsaturated oils in soybean, canola, and sunflower

Genetic alteration of histone lysine methyltransferases and their significance in renal cell carcinoma

Background Histone lysine methyltransferases (HMTs), a category of enzymes, play essential roles in regulating transcription, cellular differentiation, and chromatin construction. The genomic landscape and clinical significance of HMTs in renal cell carcinoma (RCC) remain uncovered. Methods We conducted an integrative analysis of 50 HMTs in RCC and discovered the internal relations among copy number alterations (CNAs), expressive abundance, mutations, and clinical outcome. Results We confirmed 12 HMTs with the highest frequency of genetic alterations, including seven HMTs with high-level amplification, two HMTs with somatic mutation, and three HMTs with putative homozygous deletion. Patterns of copy number and expression varied among different subtypes of RCC, including clear cell renal cell carcinoma, papillary cell carcinoma, and chromophobe renal carcinoma. Kaplan–Meier survival analysis and multivariate analysis identified that CNA or mRNA expression in some HMTs were significantly associated with shorter overall patient survival. Systematic analysis identified six HMTs (ASH1L, PRDM6, NSD1, EZH2, WHSC1L1, SETD2) which were dysregulated by genetic alterations as candidate therapeutic targets. Discussion In summary, our findings strongly evidenced that genetic alteration of HMTs may play an important role in generation and development of RCC, which lays a solid foundation for the mechanism for further research in the future

SnS2 quantum dots: facile synthesis, properties and applications in ultraviolet photodetector

Tin sulfide quantum dots (SnS2 QDs) are n-type wide band gap semiconductor. They exhibit a high optical absorption coefficient and strong photoconductive property in the ultraviolet and visible regions. Therefore, they have been found to have many potential applications, such as gas sensors, resistors, photodetectors, photocatalysts, and solar cells. However, the existing preparation methods for SnS2 QDs are complicated and require a high temperature and high pressure environment; hence they are unsuitable for large-scale industrial production. An effective method for the preparation of monodispersed SnS2 QDs at normal temperature and pressure will be discussed in this paper. The method is facile, green, and low-cost. In this work, the structure, morphology, optical, electrical, and photoelectric properties of SnS2 QDs are studied. The synthesized SnS2 QDs are homogeneous in size and exhibit good photoelectric performance. A photoelectric detector based on the SnS2 QDs is fabricated and its J-V and C-V characteristics are also studied. The detector responds under λ=365 nm light irradiation and reverse bias voltage. Its detectivity approximately stabilizes at 1011 Jones at room temperature. These results show the possible use of SnS2 QDs in photodetectors

The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer

Duanzheng Zhao,1 Libin Guo,2,* Henrique Neves,3,* Hiu-Fung Yuen,4 Shu-Dong Zhang,5 Cian M McCrudden,6 Qing Wen,5 Jin Zhang,2 Qi Zeng,4 Hang Fai Kwok,3,5,6 Yao Lin2 1College of Continuing Education, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, People’s Republic of China; 2College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, People’s Republic of China; 3Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau Special Administrative Region, People’s Republic of China; 4Institute of Molecular and Cell Biology, Biopolis Drive, Proteos, Singapore; 5Center for Cancer Research and Cell Biology, 6School of Pharmacy, Queen’s University of Belfast, Belfast, UK *These authors have contributed equally to this work Abstract: Although PTP4A3 has been shown to be a very important factor in promoting cancer progression, the role of its close family member PTP4A2 is still largely unknown. Recent reports have shown contradicting results on the role of PTP4A2 in breast cancer progression. Considering this, we aimed to investigate the prognostic value of PTP4A2 in five independent breast cancer data sets (minimum 198 patients per cohort, totaling 1,124 patients) in the Gene Expression Omnibus Database. We found that high expression of PTP4A2 was a favorable prognostic marker in all five independent breast cancer data sets, as well as in the combined cohort, with a hazard ratio of 0.68 (95% confidence interval =0.56–0.83; P<0.001). Low PTP4A2 expression was associated with estrogen receptor-negative tumors and tumors with higher histological grading; furthermore, low expression was inversely correlated with the expression of genes involved in proliferation, including MKI67 and the MCM gene family encoding the minichromosome maintenance proteins. These findings suggest that PTP4A2 may play a role in breast cancer progression by dysregulating cell proliferation. PTP4A2 expression was positively correlated with ESR1, the gene encoding estrogen receptor-alpha, and inversely correlated with EGFR expression, suggesting that PTP4A2 may be involved in these two important oncogenic pathways. Together, our results suggest that expression of PTP4A2 is a favorable prognostic marker in breast cancer. Keywords: breast cancer, PTP4A2, survival, prognostic marker, overexpression, minichromosome maintenance proteins&nbsp

Construction of a high-density genetic map for faba bean (Vicia faba L.) and quantitative trait loci mapping of seed-related traits

Faba bean (Vicia faba L.) is a valuable legume crop and data on its seed-related traits is required for yield and quality improvements. However, basic research on faba bean is lagging compared to that of other major crops. In this study, an F2 faba bean population, including 121 plants derived from the cross WY7×TCX7, was genotyped using the Faba_bean_130 K targeted next-generation sequencing genotyping platform. The data were used to construct the first ultra-dense faba bean genetic map consisting of 12,023 single nucleotide polymorphisms markers covering 1,182.65 cM with an average distance of 0.098 cM. The map consisted of 6 linkage groups, which is consistent with the 6 faba bean chromosome pairs. A total of 65 quantitative trait loci (QTL) for seed-related traits were identified (3 for 100-seed weight, 28 for seed shape, 12 for seed coat color, and 22 for nutritional quality). Furthermore, 333 candidate genes that are likely to participate in the regulation of seed-related traits were also identified. Our research findings can provide a basis for future faba bean marker-assisted breeding and be helpful to further modify and improve the reference genome

In2S3 Quantum Dots: Preparation, Properties and Optoelectronic Application

Low-dimensional semiconductors exhibit remarkable performances in many device applications because of their unique physical, electrical, and optical properties. In this paper, we report a novel and facile method to synthesize In2S3 quantum dots (QDs) at atmospheric pressure and room temperature conditions. This involves the reaction of sodium sulfide with indium chloride and using sodium dodecyl sulfate (SDS) as a surfactant to produce In2S3 QDs with excellent crystal quality. The properties of the as-prepared In2S3 QDs were investigated and photodetectors based on the QDs were also fabricated to study the use of the material in optoelectronic applications. The results show that the detectivity of the device stabilizes at ~ 1013 Jones at room temperature under 365 nm ultraviolet light irradiation at reverse bias voltage