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Lung cancer remains the most common cancer and the leading cause of cancer death worldwide. Despite effective chemotherapy and molecular-based therapies, the median and overall survival remains poor. Immune checkpoint inhibitors have changed the treatment landscape for patients with non-small cell lung cancer (NSCLC) by inhibiting negative T cell regulators, including programmed death 1 (PD-1, CD279) and programmed death ligand 1 (PD-L1, also known as B-H1, CD274) inhibitors. Nonetheless, most patients do not respond to these inhibitors. Recently, PD-L1 expression has been demonstrated to influence the anti-tumor efficacy of immune checkpoint inhibitors. However, the mechanisms of PD-L1 regulation are not clearly understood. This review thus aims to summarize the current knowledge and recent developments in the regulatory mechanisms of PD-L1 expression levels and attempts to clarify its latent function in anti-tumor activity, with the goal of guiding better designs for future NSCLC immunotherapies.

Eleven CO2 gas fields (pools) have been discovered in the Huanghua and Jiyang Depressions of Bohai Bay Basin, Eastern China. The analyses of natural gas geochemical data in the CO2 gas fields (pools) reveal the following: First, there is a positive correlation between CO2 content, δ13CCO2 values, and R/Ra values but a negative correlation between CO2 content and CH4 content; Second, the elevated δ13CCO2, R/Ra, and 40Ar/36Ar values show that CO2 is mantle-derived; Third, organic and inorganic alkane gases are both discovered in the CO2 gas fields of the Huanghua Depression, and the alkane gas in the Jiyang Depression is mainly oil-type. Taking the geological background of the region into consideration, the article concludes that the high geothermal field region, intersection part of faults, magmatic rock region, and high R/Ra values region are favorable abundance zones for CO2 gas fields (pools). Key words: Bohai Bay Basin, CO2 gas field (pool), CO2 origin, geochemical characteristics, fault, helium isotope

By measuring carbon and hydrogen isotope compositions for C1, C2 and C3 of 74 gas samples, natural gases from the Tarim Basin can be divided into six groups on the basis of their origins: (1) coal-type gas derived from coal measures; (2) coal-type gas generated from the T-J lacustrine mudstones; (3) oil-type gas derived from the Cambrian and low Ordovician marine source rocks; (4) oil-type gas from the source rocks deposited in the marine-transitional facies; (5) mixing gas between gas derived from the Carboniferous transitional source rocks and the Mesozoic humic gas, and (6) mixing gases of thermal genetic gas and little deep gas in the Southwest depression of the Tarim Basin. The δD values of methane in natural gases originating from different type kerogens are affected by both palaeo-environments of the source rock formation (kerogen types) and thermal maturity, with sedimentary environment (kerogen type) as the main controlling factor. Under the similar thermal maturity, the hydrogen isotope composition of methane is more enriched in deuterium in marine environments than lacustrine one. With the increase of thermal maturity and the increase of carbon atomic numbers of gaseous alkanes, the hydrogen isotopes become enriched in deuterium. The δD values of ethane and propane (δD2, δD3) are controlled mainly by thermal maturity and to a lesser degree by sedimentary environment of the source rock formation. The partial reversal of hydrogen isotopes for gaseous alkanes would be related to the microbial oxidation, mixing of sapropelic and humic gases and / or mixing of gases from similar kerogen sources with various thermal maturities. In the oil-type gas, the sulfate reduction reaction would result in the reversed order of δD1 and δD2 (e.g. δD1>δD2).

CORE, a trust model is proposed trying to solve agent coalition formation problem. The model characterizes an agent’s trust from two aspects of competence and reputation. In the paper, the Euclidean distance formula of vector space on competence field is used to measure the extent which an agent fitting for a particular task, and the membership function is used to characterize an agent’s reputation. At the begin of the task, appropriate agents are selected to form a coalition according to their trust value; in the process of the task, the agent’s competence gains and reputation updates; after completing the task, the model can renovate every agent’s trust according to their behavior during the coalition, which is viewed as an evidence for next task. Finally, the model is carried out by programming on the NetLogo platform.

Objectives Heart I/R may exacerbate myocardial injury by the release of massive of reactive oxygen and nitrogen species. Calpain has been proposed to play a role in the pathogenesis of heart I/R injury. However, the underlying mechanisms are still not thoroughly understood. Here we investigated the effect of μ-Calpain on heart I/R injury and elucidated the underlying mechanisms. Methods Studies were performed with I/R rats9 hearts. MDL-281703, a μ-Calpain inhibitor, was used to inhibit the activate of μ-Calpain. The cardiac function and cells apoptosis were detected. The activation of μ-Calpain, Bid and Apoptosis-inducing factor (AIF) were evaluated during the I/R protocol. Results During the I/R protocol, the 76 kDa size of fragment, which was active fragment of μ-Calpain, significantly increased. In the same time, the expression of AIF in nuclear and Bid also increased. Administration of MDL-281703 decreased cells apoptosis from 36±3.9% to 25±7.1% p Conclusions Our results suggested that μ-Calpain played a role of cells apoptosis in rats heart I/R injury. In this process, μ-Calpain regulate cardiomyocytes apoptosis via both caspase-dependent pathway (Bid) and non-caspase dependent pathway (AIF).

Objectives Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), a novel, potent PARP inhibitor, has been proved to have cardiac protective effects. However, the underlying mechanisms are still not thoroughly understood. In this study, we investigate the effect of DPQ on heart I/R injury and its potential mechanisms. Methods Studies were performed with I/R rats9 hearts. DPQ was used to inhibit the activate of PARP. The myocardial infarction size, cardiac function and cells apoptosis were detected. The activation of PARP, transcription factor nuclear factor-kappaB (NF-κB), intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and Matrix metalloproteinase-9 (MMP-9) were evaluated during the I/R protocol. Results Our data showed that DPQ could reduce the rat heart I/R injury in vivo. Heart I/R caused a significant increase in PARP activity. Administration of DPQ could decrease the activation of PARP. At the same time, administration of DPQ could decrease myocardial infarction size from 60.97±4.22% to 39.03±3.94% (p Conclusions Our results suggested that the inhibition of PARP was able to reduce heart I/R injury. The protective effects of DPQ were associated with both inflammation and Akt signalling.