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As an important principle of international environmental law, the principle of common but differentiated responsibilities (the CBDR principle) is being applied to various international environment protection regimes including environmental governance on the high seas as an important guiding principle in the law of the sea. This may be beneficial for engaging the international community to protect the high seas in solidarity. However, the application of the CBDR principle encounters difficulties, which include obstacles regarding cross-sector application, different understandings of the CBDR principle and difficulties in implementation of international instruments. This article argues that the differentiation should not depend exclusively on the traditional dichotomy of developing and developed countries but must be determined on a fluid and case-by-case basis. This suggests that the details of the differentiated responsibilities should also be context-specific rather than uniform for all States. Moreover, the implementation of the CBDR principle to address environmental problems on the high seas should be based on substantive fairness. Finally, this article makes several observations. First, the demands of developing countries in the field of maritime emission reduction should be considered. Second, obligation of capacity building and the transfer of marine technology prescribed in the BBNJ Agreement should be encouraged and implemented. Third, strengthening international cooperation in plastic pollution control on the high seas is expected. Fourth, the international community should provide developing countries with the financial support and technical assistance in persistent organic pollutants control. All of these may contribute to the protection of the high seas environment and the future realization of the sustainable development of the oceans. [ABSTRACT FROM AUTHOR]

Hosts defend against parasites through two main strategies: resistance and tolerance. These two strategies have different influences on the parasite load of the host and so have variable effects on the fitness of parasites. In this study, we investigated the strategy used by the Barn Swallow (Hirundo rustica) to defend against a hematophagous mite (Dermanyssus hirundinis) in East Asia. For the first time, we found Barn Swallows were parasitized by D. hirundinis in Asia and, in northeastern China, over 60% of broods were parasitized. We examined whether swallows with better body condition or the males with more extravagant sexually selected traits (longer tail streamers or redder ventral plumage) showed stronger resistance or tolerance to these parasites. The results showed that males with more extravagant sexual ornaments had weaker resistance (heavier brood mite load) than males with less extravagant traits; however, the heavier mite load was likely to be a byproduct of larger brood size. Moreover, the Barn Swallow population showed strong tolerance against the parasite (i.e. the brood mite load did not affect brood size or nestling body mass). It is worth noting that male swallows with redder breast plumage showed weaker tolerance (lower seasonal reproductive success) than other males. Further, we conducted experimental ectoparasite manipulations in 46 Barn Swallow nests to verify the potential effect of these parasites on the body condition of nestlings. Neither the body mass nor the hemoglobin concentration differed between the designed groups; however, the hemoglobin concentration of nestlings decreased with mite load. We concluded that the Barn Swallow population in East Asia used the tolerance strategy, rather than resistance to defend against nest mites, and the ectoparasitic mite did not appear to be a strong selective factor for reproductive success owing to the strong tolerance of the studied Barn Swallow population. [ABSTRACT FROM AUTHOR]

Intramuscular lipid deposition is important for meat quality improvement. microRNAs and their target mRNAs provide a new approach for studying the mechanism of fat deposition. The present study aimed to investigate the effect of miR-130b duplex (miR-130b-5p, miR-130b-3p) and its target gene KLF3 in regulating goat intramuscular adipocyte differentiation. Goat intramuscular preadipocytes were isolated from 7-d-old male Jianzhou big-ear goats and identified by Oil red O staining after differentiation induction. miR-130b-5p and miR-130b-3p mimics or inhibitors and their corresponding controls were transfected into goat intramuscular preadipocytes, respectively, and differentiation was induced by 50μM oleic acid for 48 h. Oil red O and Bodipy staining indicated that both miR-130b-5p and miR-130b-3p can reduce lipid droplets accumulation and triglyceride (TG) content (P < 0.01). Differentiation markers C/EBPα, C/EBPβ, PPARγ, pref1, fatty acids synthesis markers ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, AP2, SREBP1, and TG markers LPL, ATGL, HSL were assessed by qPCR. All the markers measured were downregulated by miR-130b-5p and miR-130b-3p analog (P < 0.01), suggesting that miR-130b inhibits goat intramuscular adipocyte adipogenic differentiation, fatty acids synthesis, and lipid lipolysis. To examine the mechanism of miR-130b duplex inhibition of lipid deposition, TargetScan, miRDB, and starBase were used to predict the potential targets, KLF3 was found to be the only one intersection. Furthermore, the 3ʹUTR of KLF3 was cloned, qPCR analysis and dual luciferase activity assay showed that both miR-130b-5p and miR-130b-3p could directly regulate KLF3 expression (P < 0.01). In addition, overexpression and interference of KLF3 were conducted, it was found that KLF3 positively regulated lipid droplets accumulation by Oil red O, Bodipy staining, and TG content detection (P < 0.01). Quantitative PCR result indicated that KLF3 overexpression promoted lipid droplets accumulation relative genes C/EBPβ, PPARγ, pref1, ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, SREBP1, LPL, and ATGL expression (P < 0.01). Downregulation of KLF3 inhibited the expression of genes such as C/EBPα, C/EBPβ, PPARγ, pref1, TIP47, GPAM, ADRP, AP2, LPL, and ATGL expression (P < 0.01). Taken together, these results indicate that miR-130b duplex could directly inhibit KLF3 expression, then attenuated adipogenic and TG synthesis genes expression, thus leading to its anti-adipogenic effect. [ABSTRACT FROM AUTHOR]

There are many complex optimization problems in the real world, and various evolutionary algorithms are proposed to solve them. Recently, the many-objective evolutionary algorithm using a one-by-one selection strategy (1by1EA) adopts a convergence indicator and a distribution indicator to balance convergence and diversity. However, the algorithm is too random in initialization and the fitness evaluation of solutions in the mating selection is single, which leads to poor performance in solving large-scale problems. Therefore, this paper proposes an improved method called 1by1EA-CHV by using circle chaotic mapping and a solution ranking mechanism based on the hypervolume (HV) indicator. We first map each component of solutions into a certain value space to initialize the population. Then, we calculate the contribution of each partition divided based on HV and apply the aggregation method to guide the reallocation of fitness, which achieves the ranking of solutions by using it before the old calculation method. To validate the performance, experiments compared 1by1EA-CHV with 1by1EA and other seven many-objective algorithms on large-scale functions, and the differences between these algorithmswere analyzed statistically by a non-parametric test. The results showed the superiority of 1by1EA-CHV in solving large-scale many-objective optimization problems with up to 2000 decision variables. [ABSTRACT FROM AUTHOR]

Context: Pheochromocytomas and paragangliomas (PPGLs) are being increasingly discovered by imaging performed for unrelated conditions. The genetic landscape of incidental PPGLs remains to be elucidated. Objective: We aimed to describe the genetic characteristics of PPGLs discovered incidentally in a large PPGL cohort. Methods: This retrospective cross-sectional study included 697 patients with pathology confirmed PPGLs, including 283 incidentalomas and 414 nonincidentalomas, at 2 tertiary care centers in China in 2009-2019. Tumor DNA samples were sequenced by next-generation sequencing. Identified genetic mutations were confirmed by Sanger sequencing and tested in 277 available matched blood DNA samples. Results: There was a lower proportion of patients with mutations identified (53% vs 63.3%; P = 0.0067) in incidental than nonincidental PPGLs. In incidental PPGLs, HRAS (11.7%), FGFR1 (11%), and RET (9.2%) were the top 3 mutated genes, whereas HRAS (17.9%), VHL (9.2%), and NF-1 (8.7%) exhibited the highest rate of mutations in nonincidental PPGLs. In incidental pheochromocytomas, the most frequently mutated genes were RET (10.9%), HRAS (10.4%), and VHL (8.6%), while in incidental paragangliomas, FGFR1 (32.8%), HRAS (16.4%), and EPAS1 (9.8%) topped the list. The frequency of NF-1 mutations was significantly lower in incidental than nonincidental pheochromocytomas (4.1% vs 11%; P = 0.0042), while FGFR1 mutations were far more common in incidental than nonincidental paragangliomas (32.8% vs 15.3%; P = 0.0076). Conclusion: More than half of patients with incidental PPGLs had mutations in common susceptibility genes. The search for susceptibility genes should take both the mode of discovery (incidental vs nonincidental) and tumor location (pheochromocytoma vs paraganglioma) into consideration. [ABSTRACT FROM AUTHOR]