Study of a possible structural relationship between thymopoietin and the facteur thymique serique

Background peptide chemistry, and the known 49-amino acid sequence of thymopoietin and the known 9-amino acid sequence of the facteur thymique serique (FTS) allowed the concept that Arg⁴⁹ of thymopoietin might be linked to Gln¹ of FTS in a new 58-amino acid peptide in tissue. Cleavage between Arg⁴⁹ and Gln⁵⁰ adjacent to the unique Lys⁴⁸-Arg⁴⁹ moiety could liberate thymopoietin and the [H-Gln¹]-FTS which could cyclize to FTS by the known reaction. In support of, rather than negating, this concept, synthetic FTS and the new dodecapeptide consisting of Val-Lys-Arg linked to the N-terminal of [H-Gln¹]-FTS showed comparable immune stimulating activity, $\text{in vivo}$; both peptides appeared more active than synthetic thymopoietin II.     

Modeling influenza seasonality in the tropics and subtropics

Climate drivers such as humidity and temperature may play a key role in influenza seasonal transmission dynamics. Such a relationship has been well defined for temperate regions. However, to date no models capable of capturing the diverse seasonal pattern in tropical and subtropical climates exist. In addition, multiple influenza viruses could cocirculate and shape epidemic dynamics. Here we construct seven mechanistic epidemic models to test the effect of two major climate drivers (humidity and temperature) and multi-strain co-circulation on influenza transmission in Hong Kong, an influenza epidemic center located in the subtropics. Based on model fit to long-term influenza surveillance data from 1998 to 2018, we found that a simple model incorporating the effect of both humidity and temperature best recreated the influenza epidemic patterns observed in Hong Kong. The model quantifies a bimodal effect of absolute humidity on influenza transmission where both low and very high humidity levels facilitate transmission quadratically; the model also quantifies the monotonic but nonlinear relationship with temperature. In addition, model results suggest that, at the population level, a shorter immunity period can approximate the co-circulation of influenza virus (sub)types. The basic reproductive number R₀ estimated by the best-fit model is also consistent with laboratory influenza survival and transmission studies under various combinations of humidity and temperature levels. Overall, our study has developed a simple mechanistic model capable of quantifying the impact of climate drivers on influenza transmission in (sub)tropical regions. This model can be applied to improve influenza forecasting in the (sub)tropics in the future.     

Two uvs genes of Aspergillus nidulans with different functions in error-prone repair: uvsI, active in mutation-specific reversion, and uvsC, a recA homolog, required for all UV mutagenesis

Two genes of Aspergillus nidulans are known to function in UV mutagenesis, but have been assigned to different epistasis groups: uvsC, which is also required for meiosis and mitotic recombination, and uvsI, which may have no other function. To clarify their role in error-prone repair and to investigate their interaction, uvsI and uvsC single and uvsI;uvsC double mutant strains were further tested for mutagen sensitivities and characterized for effects on mutation. Spontaneous and induced frequencies were compared in forward and reverse mutation assays. All results confirmed that uvsI and uvsC are members of different epistasis groups, and demonstrated that these uvs mutants have very different defects in UV mutagenesis. The uvsI strains showed wild-type frequencies in all forward mutation tests, but greatly reduced spontaneous and UV-induced reversion of some, but not other, point mutations. In contrast, uvsC had similar effects in all assay systems: namely pronounced mutator effects and greatly reduced UV mutagenesis. Interestingly, the uvsI;uvsC double mutant strains differed from both single mutants; they clearly showed synergism for all types of reversion tested: none were ever obtained spontaneously, nor after induction by UV or EMS (ethylmethane sulfonate). Based on these results, we conclude that uvsI is active in a mutation-specific, specialized error-prone repair process in Aspergillus. In contrast, uvsC, which is now known to show sequence homology to recA, has a basic function in mutagenic UV repair in addition to recombinational repair, similar to recA of Escherichia coli.     

Thermolabile Triose Phosphate Isomerase in a Psychrophilic Clostridium

The psychrophile Clostridium sp. strain 69 contains a thermolabile triose phosphate isomerase which is inactivated rapidly in vitro and in vivo at 32 C.     

Tumour‐derived exosomal miR‐3473b promotes lung tumour cell intrapulmonary colonization by activating the nuclear factor‐κB of local fibroblasts

Tumour‐derived exosomes have been shown to induce pre‐metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC‐derived exosomes were mainly engulfed by lung fibroblasts and led to the NF‐κB signalling activation. Further studies indicated that the exosomal miR‐3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR‐3473b could reverse the exosome‐mediated NF‐κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR‐3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.     

Investigation of the Effects of Squalene and Squalene Epoxides on the Homeostasis of Coenzyme Q10 in Rats by UPLC‐Orbitrap MS

Squalene has been used as a dietary supplement for a long history due to its potential cancer‐preventive function. However, the mechanism has not been investigated in detail yet. Therefore, the aim of this study is to see if the plasma coenzyme Q10 (CoQ10) level will be altered by gavage of squalene and oxidosqualenes to rats. In the present work, a sensitive and simple high‐performance analytical method based on ultra‐high‐performance liquid chromatography coupled with an Orbitrap mass spectrometry (UPLC‐Orbitrap‐MS) was developed for the quantification of CoQ10 in rat plasma. Coenzyme Q9 (CoQ9) was employed as the internal standard. CoQ10 was determined after acetonitrile‐mediated plasma protein precipitation using UPLC‐Orbitrap‐MS in negative ion mode. Intragastric administration of squalene and the two squalene epoxides into rats once daily for several days elevated the level of CoQ10 in their plasma, but there was no significant difference between high‐dose (286 mg/kg) and low‐dose (143 mg/kg) groups. Intragastric administration of squalene once a day for 5 consecutive days and oxidosqualenes once a day for 3 consecutive days is necessary for reaching the steady‐state level of CoQ10. Our present findings indicate that squalene and oxidosqualenes may be useful for stimulating the synthesis of CoQ10 in rats.     

An Antiaging Electrolyte Additive for High‐Energy‐Density Lithium‐Ion Batteries

High‐capacity Li‐rich layered oxide cathodes along with Si‐incorporated graphite anodes have high reversible capacity, outperforming the electrode materials used in existing commercial products. Hence, they are potential candidates for the development of high‐energy‐density lithium‐ion batteries (LIBs). However, structural degradation induced by loss of interfacial stability is a roadblock to their practical use. Here, the use of malonic acid‐decorated fullerene (MA‐C₆₀) with superoxide dismutase activity and water scavenging capability as an electrolyte additive to overcome the structural instability of high‐capacity electrodes that hampers the battery quality is reported. Deactivation of PF₅ by water scavenging leads to the long‐term stability of the interfacial structures of electrodes. Moreover, an MA‐C₆₀‐added electrolyte deactivates the reactive oxygen species and constructs an electrochemically robust cathode‐electrolyte interface for Li‐rich cathodes. This work paves the way for new possibilities in the design of electrolyte additives by eliminating undesirable reactive substances and tuning the interfacial structures of high‐capacity electrodes in LIBs.