C. elegans fatty acid two-hydroxylase regulates intestinal homeostasis by affecting heptadecenoic acid production

Background/Aims: The hydroxylation of fatty acids at the C-2 position is the first step of fatty acid α-oxidation and generates sphingolipids containing 2-hydroxy fatty acyl moieties. Fatty acid 2-hydroxylation is catalyzed by Fatty acid 2-hydroxylase (FA2H) enzyme. However, the precise roles of FA2H and fatty acid 2-hydroxylation in whole cell homeostasis still remain unclear. Methods: Here we utilize Caenorhabditis elegans as the model and systemically investigate the physiological functions of FATH-1/C25A1.5, the highly conserved worm homolog for mammalian FA2H enzyme. Immunostaining, dye-staining and translational fusion reporters were used to visualize FATH-1 protein and a variety of subcellular structures. The “click chemistry” method was employed to label 2-OH fatty acid in vivo. Global and tissue-specific RNAi knockdown experiments were performed to inactivate FATH-1 function. Lipid analysis of the fath-1 deficient mutants was achieved by mass spectrometry. Results: C. elegans FATH-1 is expressed at most developmental stages and in most tissues. Loss of fath-1 expression results in severe growth retardation and shortened lifespan. FATH-1 function is crucially required in the intestine but not the epidermis with stereospecificity. The “click chemistry” labeling technique showed that the FATH-1 metabolites are mainly enriched in membrane structures preferable to the apical side of the intestinal cells. At the subcellular level, we found that loss of fath-1 expression inhibits lipid droplets formation, as well as selectively disrupts peroxisomes and apical endosomes. Lipid analysis of the fath-1 deficient animals revealed a significant reduction in the content of heptadecenoic acid, while other major FAs remain unaffected. Feeding of exogenous heptadecenoic acid (C17: 1), but not oleic acid (C18: 1), rescues the global and subcellular defects of fath-1 knockdown worms. Conclusion: Our study revealed that FATH-1 and its catalytic products are highly specific in the context of chirality, C-chain length, spatial distribution, as well as the types of cellular organelles they affect. Such an unexpected degree of specificity for the synthesis and functions of hydroxylated FAs helps to regulate protein transport and fat metabolism, therefore maintaining the cellular homeostasis of the intestinal cells. These findings may help our understanding of FA2H functions across species, and offer potential therapeutical targets for treating FA2H-related diseases

Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study

BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size

Fully corrective boosting with arbitrary loss and regularization

We propose a general framework for analyzing and developing fully corrective boosting-based classifiers. The framework accepts any convex objective function, and allows any convex (for example, lp-norm, p ≥ 1) regularization term. By placing the wide variety of existing fully corrective boosting-based classifiers on a common footing, and considering the primal and dual problems together, the framework allows direct com- parison between apparently disparate methods. By solving the primal rather than the dual the framework is capable of generating efficient fully-corrective boosting algorithms without recourse to sophisticated convex optimization processes. We show that a range of additional boosting-based algorithms can be incorporated into the framework despite not being fully corrective. Finally, we provide an empirical analysis of the per- formance of a variety of the most significant boosting-based classifiers on a few machine learning benchmark datasets.Chunhua Shen, Hanxi Li, Anton van den Henge

Developing metro-based accessibility: Three aspects of China’s Rail+Property practice

Populous Chinese cities have invested heavily in metro systems and planned proactively for transit-oriented development. Rail plus property (R+P) programs, where metro corporations engage in, and even orchestrate real estate development in or around rail station areas, have been recurrently reported among these cities. However, careful assessment of these programs is still rare in the existing literature. Built upon multiple R+P programs led by Shenzhen Metro Cooperation and/or Hong Kong Mass Transit Railway Cooperation, this article fathoms the rationale for R+P programs in Mainland China, the obstacles for oversea private investors’ participation and the balance between profit making and social goods supply. It finds that R+P programs serve as alternative funding sources for expensive metro projects. It decreases municipal governments’ cash flow contribution to those projects, which is mandated by the central government. In addition, local business environment for R+P projects has disadvantaged private sector participation, especially those private investors from overseas. Furthermore, public subsidy to local metro corporations is likely to persist as R+P programs have not been designed for economic value maximization; rather, they are in place because (1) they reduce the cash flow burden of the municipal government; (2) they are tasked by the municipal government to produce a considerable number of affordable public housing

Physiological and Transcriptomic Analysis Revealed the Molecular Mechanism of <i>Pinus koraiensis</i> Responses to Light

Korean pine (Pinus koraiensis Sieb. et Zucc.), as the main tree species in northeast China, has important economic and ecological values. Currently, supplementary light has been widely used in plant cultivation projects. However, the studies about different supplementary light sources on the growth and development of Korean pine are few. In this study, the one with no supplementary light was used as the control, and two kinds of light sources were set up: light-emitting diode (LED) and incandescent lamp, to supplement light treatment of Korean pine. The spectrum and intensity of these two light sources were different. The results showed that the growth and physiological–biochemical indicators were significantly different under different supplementary light treatments. The biomass of supplementary light treatment was significantly lower than the control. Compared with the control, IAA and GA were lower, and JA, ABA, ZT, and ETH were higher under supplementary light conditions. Photosynthetic parameters in supplementary light conditions were significantly lower than the control. Supplemental light induces chlorophyll a, chlorophyll b, total chlorophyll, and carotenoid accumulation. From RNA-seq data, differentially expressed genes (DEGs) were observed in all the comparison groups, and there were 487 common DEGs. The expression levels of DEGs encoding transcription factors were also changed. According to GO and KEGG analysis, the plant hormone signal transduction, circadian rhythm-plant, and flavonoid biosynthesis pathways were the most enriched. These results provided a theoretical basis for the response of Korean pine to different supplementary lights