Whether species demography and diversification are driven primarily by extrinsic environmental changes such as climatic oscillations in the Quaternary or by intrinsic biological interactions like ...coevolution between antagonists is a matter of active debate. In fact, their relative importance can be assessed by tracking past population fluctuations over considerable time periods.
We applied the pairwise sequentially Markovian coalescent approach on the genomes of 11 temperate Juglans species to estimate trajectories of changes in effective population size (N
e) and used a Bayesian-coalescent based approach that simultaneously considers multiple genomes (G-PhoCS) to estimate divergence times between lineages.
N
e curves of all study species converged 1.0 million yr ago, probably reflecting the time when the walnut genus last shared a common ancestor. This estimate was confirmed by the G-PhoCS estimates of divergence times. But all species did not react similarly to the dramatic climatic oscillations following early Pleistocene cooling, so the timing and amplitude of changes in N
e differed among species and even among conspecific lineages.
The population histories of temperate walnut species were not driven by extrinsic environmental changes alone, and a key role was probably played by species-specific factors such as coevolutionary interactions with specialized pathogens.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Purpose
Oxidative stress and neuronal apoptosis play key roles in traumatic brain injury. We investigated the protective effects of astaxanthin against traumatic brain injury and its ...underlying mechanisms of action.
Experimental Approach
A weight‐drop model of traumatic brain injury in vivo and hydrogen peroxide exposure in vitro model were established. Brain oedema, behaviour tests, western blot, biochemical analysis, lesion volume, histopathological study and cell viability were performed.
Key Results
Astaxanthin significantly reduced oxidative insults on Days 1, 3 and 7 after traumatic brain injury. Neuronal apoptosis was also ameliorated on Day 3. Additionally, astaxanthin improved neurological functions up to 3 weeks after traumatic brain injury. Astaxanthin treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor‐erythroid 2‐related factor 2 (NRF2/Nrf2) and sirtuin 1 (SIRT1), while it down‐regulated the phosphorylation of apoptosis signal‐regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by siRNA injection reversed the beneficial effects of astaxanthin against traumatic brain injury. Additionally, Nrf2 knockout prevented the neuroprotective effects of astaxanthin in traumatic brain injury. In contrast, overexpression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after traumatic brain injury. Moreover, inhibiting SIRT1 by EX527 dramatically inhibited the neuroprotective effects of astaxanthin and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro.
Conclusion and Implications
Astaxanthin improved the neurological functions and protected the brain from injury after traumatic brain injury, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signalling pathway and might be a new candidate to ameliorate traumatic brain injury.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Ecological interactions among plants, insect herbivores, and parasitoids are pervasive in nature and play important roles in community assembling, but the codiversification of tri‐trophic ...interactions has received less attention. Here we compare pairwise codiversification patterns between a set of 22 fig species, their herbivorous pollinating and galling wasps, and their parasitoids. The parasitoid phylogeny showed significant congruence and more cospeciation events with host insects phylogeny than with host plants. These results suggest that parasitoid phylogeny and speciation is more closely related to their host insects than to their host plants. The pollinating wasps hosted more parasitoid species than gallers and indicated a more intense interspecific competition among parasitoids associated with pollinators. Closer matching and fewer evolutionary host shifts were found between parasitoids and galler hosts than between parasitoids and pollinator hosts. These results suggest that interspecific competition among parasitoids, rather than resource availability of host wasps, is the main driver of the codiversification pattern in this community. Therefore, our study highlights the important role of interspecific competition among high trophic level insects in plant–insect tri‐trophic community assembling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Anti‐PD‐L1 monoclonal antibody has achieved substantial success in tumor immunotherapy by T‐cells activation. However, the excessive accumulation of extracellular matrix components induced by ...unsatisfactory T‐cells infiltration and poor tumor penetration of antibodies make it challenging to realize efficient tumor immunotherapy. Herein, a peptide‐based bispecific nanoblocker (BNB) strategy is reported for in situ construction of CXCR4/PD‐L1 targeted nanoclusters on the surface of tumor cells that are capable of boosting T‐cells infiltration through CXCR4 blockage and enhancing T‐cells activation by PD‐L1 occupancy, ultimately realizing high‐performance tumor immunotherapy. Briefly, the BNB strategy selectively recognizes and bonds CXCR4/PD‐L1 with deep tumor penetration, which rapidly self‐assembles into nanoclusters on the surface of tumor cells. Compared to the traditional bispecific antibody, BNB exhibits an intriguing metabolic behavior, that is, the elimination half‐life (t1/2) of BNB in the tumor is 69.3 h which is ≈50 times longer than that in the plasma (1.4 h). The higher tumor accumulation and rapid systemic clearance overcome potential systemic side effects. Moreover, the solid tumor stress generated by excessive extracellular matrix components is substantially reduced to 44%, which promotes T‐cells infiltration and activation for immunotherapy efficacy. Finally, these findings substantially strengthen and extend clinical applications of PD‐1/PD‐L1 immunotherapy.
A peptide‐based bispecific nanoblocker strategy is developed for in situ construction of CXCR4/PD‐L1 targeted nanoclusters on the surface of tumor cells, which enables boosted T‐cells infiltration by CXCR4 blockage and enhanced T‐cells activation by PD‐L1 occupancy, ultimately realizing high‐performance tumor immunotherapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
At present, phenolic acid derivatives and triazole derivatives have a good antifungal effect, which has attracted widespread attention. A series of novel phenolic acid triazole derivatives were ...synthesized, and their structures were characterized by IR, MS, NMR, and X-ray crystal diffraction. Compound methyl 4-(2-bromoethoxy)benzoate, methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate, 4-(2-(1H-1,2,4-triazol-1-yl)ethoxy)benzoic acid and 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)-3-methoxybenzoic acid crystallize in the monoclinic system with space group P21/n, the monoclinic system with space group P21, the monoclinic system with space group P21 and the orthorhombic system with space group Pca21, respectively. At a concentration of 100 μg/mL and 200 μg/mL, the antifungal activity against seven plant pathogen fungi was determined. Compound methyl 4-(2-bromoethoxy)benzoate has the best inhibitory effect on Rhizoctonia solani AG1, and the inhibitory rate reached 88.6% at 200 μg/mL. The inhibitory rates of compound methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate against Fusarium moniliforme and Sphaeropsis sapinea at a concentration of 200 μg/mL were 76.1% and 75.4%, respectively, which were better than that of carbendazim.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The wild yeast Saccharomyces paradoxus has become a new model in ecology and evolutionary biology. Different lineages of S. paradoxus have been recognized across the world, but the distribution and ...genetic diversity of the species remain unknown in China, where the origin of its sibling species S. cerevisiae lies. In this study, we investigated the ecological and geographic distribution of S. paradoxus through an extensive field survey in China and performed population genomic analysis on a set of S. paradoxus strains, including 27 strains, representing different geographic and ecological origins within China, and 59 strains representing all the known lineages of the species recognized in the other regions of the world so far. We found two distinct lineages of S. paradoxus in China. The majority of the Chinese strains studied belong to the Far East lineage, and six strains belong to a novel highly diverged lineage. The distribution of these two lineages overlaps ecologically and geographically in temperate to subtropical climate zones in China. With the addition of the new China lineage, the Eurasian population of S. paradoxus exhibits higher genetic diversity than the American population. We observed more possible lineage‐specific introgression events from the Eurasian lineages than from the American lineages. Our results expand the knowledge on ecology, genetic diversity, biogeography, and evolution of S. paradoxus.
Take away
S. paradoxus is distributed in temperate to subtropical climate zones in China.
A novel highly diverged ancient lineage of S. paradoxus is identified.
S. paradoxus exhibits higher genetic diversity in Eurasia than in America.
Saccharomyces paradoxus is distributed in temperate to subtropical climate zones in China. Chinese S. paradoxus strains cluster with the Far East lineage and a novel highly diverged lineage. The Eurasian population of S. paradoxus exhibits higher genetic diversity and more possible HGT/introgression events than the American population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
• Interactions between mutualists, competitors, and antagonists have contrasting ecological effects that, sustained over generations, can influence micro- and macroevolution. Dissimilar benefits and ...costs for these interactions should cause contrasting co-diversification patterns between interacting clades, with prevalent co-speciation by mutualists, association loss by competitors, and host switching by antagonists.
• We assessed these expectations for a local assemblage of 26 fig species (Moraceae: Ficus), 26 species of mutualistic (pollinating), and 33 species of parasitic (galling) wasps (Chalcidoidea). Using newly acquired gene sequences, we inferred the phylogenies for all three clades. We then compared the three possible pairs of phylogenies to assess phylogenetic congruence and the relative frequencies of co-speciation, association duplication, switching, and loss.
• The paired phylogenies of pollinators with their mutualists and competitors were significantly congruent, unlike that of figs and their parasites. The distributions of macroevolutionary events largely agreed with expectations for mutualists and antagonists. By contrast, that for competitors involved relatively frequent association switching, as expected, but also unexpectedly frequent co-speciation. The latter result likely reflects the heterogeneous nature of competition among fig wasps.
• These results illustrate the influence of different interspecific interactions on co-diversification, while also revealing its dependence on specific characteristics of those interactions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
•High-intensity ultrasound caused oxidation and aggregation of shrimp MP.•High-intensity ultrasound improved functional properties of shrimp MP.•High-intensity ultrasound improved gelling properties ...of shrimp MP.•High-intensity ultrasound enhanced viscoelasticity of shrimp-based surimi.
The effects of high-intensity ultrasound on the physicochemical and gelling properties of Litopenaeus vannamei (L. vannamei) myofibrillar protein (MP) were investigated. MP solutions were subjected to ultrasound treatment (power 100 W, 300 W, and 500 W). It was found that the carbonyl and free amino contents of MP increased significantly with increasing ultrasound power, accompanied by enhanced emulsification properties. The increase of free radical and carbonyl content indicated that ultrasound induced the oxidation of MP. With the increase of ultrasound power, it was found that the total sulfhydryl content of the shrimp MP decreased, but the surface hydrophobicity increased significantly, which might be closely related to the conformational changes of MP. Meanwhile, a significant increase of β-sheet but a decrease of α-helix in the secondary structure of MP was observed with increasing ultrasound power, indicating that ultrasound treatment induced the stretching and flexibility of MP molecules. SDS-PAGE showed that L. vannamei MP consisted of myosin heavy chain, actin, myosin light chain, paramyosin and tropomyosin. Ultrasound treatment could lead to some degree of oxidative aggregation of MP. The results of rheological properties indicated that ultrasound treatment enhanced the viscoelasticity of MP and further improved the gel strength of MP gel. This study can provide a theoretical basis for the functional modification of shrimp MP and the processing of its surimi products.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide ...application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.
Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity ...on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.
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