Multi-actor multi-criteria sustainability assessment framework for energy and industrial systems in life cycle perspective under uncertainties. Part 1: weighting method

Purpose

Life cycle sustainability assessment is meaningful for the decision-makers/stakeholders to select the most sustainable option among multiple alternatives; however, there are usually various severe uncertainty problems in sustainability-oriented decision-making, i.e., the vagueness and ambiguity that existed in human judgments and the lack of information. This study aims at developing a novel life cycle multi-criteria sustainability assessment method for helping the decision-makers/stakeholders to determine the sustainability level of the industrial and energy systems. In part 1, an improved interval analytic hierarchy process (AHP) which allows multiple decision-makers/stakeholders to participate in the decision-making was developed to determine the weights of the criteria which were used in life cycle sustainability assessment.

Methods

It is usually difficult for the decision-makers/stakeholders to use the numbers from 1 to 9 and their reciprocals for determining the comparison matrix when using the traditional AHP method for weight calculation, because human judgments usually involve various uncertainties. In order to the overcome this weak point of the traditional AHP, an improved AHP, so-called interval AHP, in which, multiple decision-makers/stakeholders are allowed to participate in the decision-making and allowed to use interval numbers instead of crisp numbers to establish the comparison matrix for determining the weights of the criteria for life cycle sustainability assessment, has been developed.

Results and discussion

The proposed method was used to determine the weights of the four aspects for life cycle sustainability assessment including economic, safety, social, and environmental aspects. Five representative stakeholders were invited to participate in the decision-making. After Monte Carlo simulation, the final weights of the four aspects have been determined with the proposed interval AHP.

Conclusions and perspectives

An interval AHP method was developed for determining the weights of the criteria for life cycle sustainability assessment; the decision-makers are allowed to use interval numbers to establish the comparison matrix for weight calculation. The weighting coefficients determined by Monte Carlo method can accurately reflect the preferences and willingness of multi-actor comparing with the traditional AHP method. This paper merely presents a novel method to calculate the weights of the criteria for life cycle sustainability assessment, but the method for determining the sustainability performance has been presented in part 2.

     

Bacterial xenophagy and its possible role in cancer: A potential antimicrobial strategy for cancer prevention and treatment

Macroautophagy/autophagy is a conserved catabolic process through which cellular excessive or dysfunctional proteins and organelles are transported to the lysosome for terminal degradation and recycling. Over the past few years increasing evidence has suggested that autophagy is not only a simple metabolite recycling mechanism, but also plays a critical role in the removal of intracellular pathogens such as bacteria and viruses. When autophagy engulfs intracellular pathogens, the pathway is called ‘xenophagy’ because it leads to the elimination of foreign microbes. Recent studies support the idea that xenophagy can be modulated by bacterial infection. Meanwhile, convincing evidence indicates that xenophagy may be involved in malignant transformation and cancer therapy. Xenophagy can suppress tumorigenesis, particularly during the early stages of tumor initiation. However, in established tumors, xenophagy may also function as a prosurvival pathway in response to microenvironment stresses including bacterial infection. Therefore, bacterial infection-related xenophagy may have an effect on tumor initiation and cancer treatment. However, the role and machinery of bacterial infection-related xenophagy in cancer remain elusive. Here we will discuss recent developments in our understanding of xenophagic mechanisms targeting bacteria, and how they contribute to tumor initiation and anticancer therapy. A better understanding of the role of xenophagy in bacterial infection and cancer will hopefully provide insight into the design of novel and effective therapies for cancer prevention and treatment.     

Long‐term administration of pyridostigmine attenuates pressure overload‐induced cardiac hypertrophy by inhibiting calcineurin signalling

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload‐induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β‐myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1.     

The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain metastasis in patients with non-small cell lung cancer

Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10, ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC patients. Further, we evaluated the potential associations of these genes with subsequent BM development. Lung cancer cell lines stably transfected with ATG16L1: rs2241880 (T300A) were established. Mouse models of brain metastasis were developed using cells transfected with ATG16L1–300T or ATG16L1–300A. ATG10: rs10036653 and ATG16L1: rs2241880 were significantly associated with a decreased risk of BM (respective hazard ratios [HRs]=0.596, 95% confidence interval [CI] 0.398–0.894, P = 0.012; and HR = 0. 655, 95% CI 0.438–0.978, P = 0.039, respectively). ATG12: rs26532 was significantly associated with an increased risk of BM (HR=1.644, 95% CI 1.049–2.576, P = 0.030). Invasion and migration assays indicated that transfection with ATG16L1–300T (vs. 300A) stimulated the migration of A549 cells. An in vivo metastasis assay revealed that transfection with ATG16L1–300T (vs. 300A) significantly increased brain metastasis. Our results indicate that genetic variations in autophagy-related genes can predict BM and that genome analysis would facilitate stratification of patients for BM prevention trials.