Synthesis,structure–activity relationship and molecular docking of 3-oxoaurones and 3-thioaurones as acetylcholinesterase and butyrylcholinesterase inhibitors

The present study describes efficient and facile syntheses of varyingly substituted 3-thioaurones from the corresponding 3-oxoaurones using Lawesson’s reagent and phosphorous pentasulfide. In comparison, the latter methodology was proved more convenient, giving higher yields and required short and simple methodology. The structures of synthetic compounds were unambiguously elucidated by IR, MS and NMR spectroscopy. All synthetic compounds were screened for their inhibitory potential against in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Molecular docking studies were also performed in order to examine their binding interactions with AChE and BChE human proteins. Both studies revealed that some of these compounds were found to be good inhibitors against AChE and BChE.     

Synthesis of 3′,4′-difluoro-3′-deoxyribonucleosides and its evaluation of the biological activities: Discovery of a novel type of anti-HCV agent 3′,4′-difluorocordycepin

Upon reacting 3′,4′-unsaturated cytosine (8 and 9) and adenine nucleosides (13 and 14) with XeF₂/BF₃·OEt₂, the respective novel 3′,4′-difluoro-3′-deoxyribofuranosyl nucleosides (10–12 and 15–18) could be obtained. Formation of anti-adducts (11, 16 and 18) revealed that the fluorination involved oxonium ions as incipient intermediates. TBDMS-protected 3′,4′-unsaturated adenosine provided the β-face adducts as sole stereoisomers whereas α-face-selectivity was observed with the TBDPS-protected adenosine 14. The evaluation of the novel 3′-deoxy-3′,4′-difluororibofuranosylcytosine-(19–21) and adenine nucleosides (22–25) against antitumor and antiviral activities revealed that 3′,4′-difluorocordycepin (24) was found to possess anti-HCV activity. The SI of 24 was comparable to that of the anti-HCV drug ribavirin. However, sofosbuvir, FDA-approved novel anti-HCV drug, showed better SI value. Our finding revealed that the introduction of the fluoro-substituent into the 4′-position of cordycepin derivatives decreased the cytotoxicity to the host cell with retention of the antiviral activity.     

Study on the interaction between 4-(1H-indol-3-yl)-2-(p-tolyl)quinazoline-3-oxide and human serum albumin

An organic small-molecular drug, 4-(1H-indol-3-yl)-2-(p-tolyl)quinazoline-3-oxide 1a was synthesized. It was employed to investigate the binding interaction and mechanism with human serum albumin (HSA). The experimental results indicated that the fluorescence quenching of HSA by 1a is a static quenching process and formation 1a-HSA complex. The site competition experiments revealed that the combination of 1a on HSA are hydrophobic interactions in the IIA domain and hydrogen bonds in IIIA domain of HSA, and the hydrophobic interactions of 1a on HSA are stronger than that of hydrogen bonds. These results were also confirmed by molecular docking theoretic analysis and ANS-hydrophobic fluorescent probe experiment. Synchronous fluorescence experiments showed that the polarity of HSA microenvironment was increase in the interaction process of 1a with HSA. The results of binding distance explored indicated that the combination distance between 1a and HSA is 3.63 nm, which is between 0.5R₀ and 1.5R₀, revealing the energy transfer between HSA and 1a is non-radiative. These results are very helpful for people to screen out high efficient indoloquinazoline drugs.     

Why did heterospory evolve?

The primitive land plant life cycle featured the production of spores of unimodal size, a condition called homospory. The evolution of bimodal size distributions with small male spores and large female spores, known as heterospory, was an innovation that occurred repeatedly in the history of land plants. The importance of desiccation‐resistant spores for colonization of the land is well known, but the adaptive value of heterospory has never been well established. It was an addition to a sexual life cycle that already involved male and female gametes. Its role as a precursor to the evolution of seeds has received much attention, but this is an evolutionary consequence of heterospory that cannot explain the transition from homospory to heterospory (and the lack of evolutionary reversal from heterospory to homospory). Enforced outcrossing of gametophytes has often been mentioned in connection to heterospory, but we review the shortcomings of this argument as an explanation of the selective advantage of heterospory. Few alternative arguments concerning the selective forces favouring heterospory have been proposed, a paucity of attention that is surprising given the importance of this innovation in land plant evolution. In this review we highlight two ideas that may lead us to a better understanding of why heterospory evolved. First, models of optimal resource allocation – an approach that has been used for decades in evolutionary ecology to help understand parental investment and other life‐history patterns – suggest that an evolutionary increase in spore size could reach a threshold at which small spores yielding small, sperm‐producing gametophytes would return greater fitness per unit of resource investment than would large spores and bisexual gametophytes. With the advent of such microspores, megaspores would evolve under frequency‐dependent selection. This argument can account for the appearance of heterospory in the Devonian, when increasingly tall and complex vegetative communities presented competitive conditions that made large spore size advantageous. Second, heterospory is analogous in many ways to anisogamy. Indeed, heterospory is a kind of re‐invention of anisogamy within the context of a sporophyte‐dominant land plant life cycle. The evolution of anisogamy has been the subject of important theoretical and empirical investigation. Recent work in this area suggests that mate‐encounter dynamics set up selective forces that can drive the evolution of anisogamy. We suggest that similar dispersal and mating dynamics could have underlain spore size differentiation. The two approaches offer predictions that are consistent with currently available data but could be tested far more thoroughly. We hope to re‐establish attention on this neglected aspect of plant evolutionary biology and suggest some paths for empirical investigation.     

MoS2‐Based All‐Purpose Fibrous Electrode and Self‐Powering Energy Fiber for Efficient Energy Harvesting and Storage

Here an all‐purpose fibrous electrode based on MoS₂ is demonstrated, which can be employed for versatile energy harvesting and storage applications. In this coaxial electrode, ultrathin MoS₂ nanofilms are grown on TiO₂ nanoparticles coated carbon fiber. The high electrochemical activity of MoS₂ and good conductivity of carbon fiber synergistically lead to the remarkable performances of this novel composite electrode in fibrous dye‐sensitized solar cells (showing a record‐breaking conversion efficiency of 9.5%) and high‐capacity fibrous supercapacitors. Furthermore, a self‐powering energy fiber is fabricated by combining a fibrous dye‐sensitized solar cell and a fibrous supercapacitor into a single device, showing very fast charging capability (charging in 7 s under AM1.5G solar illumination) and an overall photochemical‐electricity energy conversion efficiency as high as 1.8%. In addition, this wire‐shaped electrode can also be used for fibrous Li‐ion batteries and electrocatalytic hydrogen evolution reactions. These applications indicate that the MoS₂‐based all‐purpose fibrous electrode has great potential for the construction of high‐performance flexible and wearable energy devices.     

Ultrafine Metal Nanoparticles/N‐Doped Porous Carbon Hybrids Coated on Carbon Fibers as Flexible and Binder‐Free Water Splitting Catalysts

By employing in situ reduction of metal precursor and metal‐assisted carbon etching process, this study achieves a series of ultrafine transition metal‐based nanoparticles (Ni–Fe, Ni–Mo) embedded in N‐doped carbon, which are found efficient catalysts for electrolytic water splitting. The as‐prepared hybrid materials demonstrate outstanding catalytic activities as non‐noble metal electrodes rendered by the synergistic effect of bimetal elements and N‐dopants, the improved electrical conductivity, and hydrophilism. Ni/Mo₂C@N‐doped porous carbon (NiMo‐polyvinylpyrrolidone (PVP)) and NiFe@N‐doped carbon (NiFe‐PVP) produce low overpotentials of 130 and 297 mV at a current density of 10 mA cm^?2 as catalysts for hydrogen evolution reaction and oxygen evolution reaction, respectively. In addition, these binder‐free electrodes show long‐term stability. Overall water splitting is also demonstrated based on the couple of NiMo‐PVP||NiFe‐PVP catalyzer. This represents a simple and effective synthesis method toward a new type of nanometal–carbon hybrid electrodes.     

Evolutionary emergence and maintenance of horizontally transmitted mutualism that do not rely on the supply of standing variation in symbiont quality

Mutualism based on reciprocal exchange of costly services must avoid exploitation by ‘free‐rides’. Accordingly, hosts discriminate against free‐riding symbionts in many mutualistic relationships. However, as the selective advantage of discriminators comes from the presence of variability in symbiont quality that they eliminate, discrimination and thus mutualism have been considered to be maintained with exogenous supply of free‐riders. In this study, we tried to resolve the ‘paradoxical’ co‐evolution of discrimination by hosts and cooperation by symbionts, by comparing two different types of discrimination: ‘one‐shot’ discrimination, where a host does not reacquire new symbionts after evicting free‐riders, and ‘resampling’ discrimination, where a host does from the environment. Our study shows that this apparently minor difference in discrimination types leads to qualitatively different evolutionary outcomes. First, although it has been usually considered that the benefit of discriminators is derived from the variability of symbiont quality, the benefit of a certain type of discriminators (e.g. one‐shot discrimination) is proportional to the frequency of free‐riders, which is in stark contrast to the case of resampling discrimination. As a result, one‐shot discriminators can invade the free‐rider/nondiscriminator population, even if standing variation for symbiont quality is absent. Second, our one‐shot discriminators can also be maintained without exogenous supply of free‐riders and hence is free from the paradox of discrimination. Therefore, our result indicates that the paradox is not a common feature of evolution of discrimination but is a problem of specific types of discrimination.     

A testis‐specific gene within a widely expressed gene: Contrasting evolutionary patterns of two differentially expressed mammalian proteins encoded by a single gene,CAMK4

Understanding the patterns of genetic variations within fertility‐related genes and the evolutionary forces that shape such variations is crucial in predicting the fitness landscapes of subsequent generations. This study reports distinct evolutionary features of two differentially expressed mammalian proteins [CaMKIV (Ca²⁺/calmodulin‐dependent protein kinase IV) and CaS (calspermin)] that are encoded by a single gene, CAMK4. The multifunctional CaMKIV, which is expressed in multiple tissues including testis and ovary, is evolving at a relatively low rate (0.46–0.64 × 10^?9 nucleotide substitutions/site/year), whereas the testis‐specific CaS gene, which is predominantly expressed in post‐meiotic cells, evolves at least three to four times faster (1.48–1.98 × 10^?9 substitutions/site/year). Concomitantly, maximum‐likelihood‐based selection analyses revealed that the ubiquitously expressed CaMKIV is constrained by intense purifying selection and, therefore, remained functionally highly conserved throughout the mammalian evolution, whereas the testis‐specific CaS gene is under strong positive selection. The substitution rates of different mammalian lineages within both genes are positively correlated with GC content, indicating the possible influence of GC‐biased gene conversion on the estimated substitution rates. The observation of such unusually high GC content of the CaS gene (≈74%), particularly in the lineage that comprises the bovine species, suggests the possible role of GC‐biased gene conversion in the evolution of CaS that mimics positive selection.     

Laetoli toes andAustralopithecus afarensis

The probable misfit between feet, particularly toes II–V, of 3.0-million-year-oldAustralopithecus afarensis from Hadar, Ethiopia, and the 3.5-million-year-old hominid footprints at Site G, Laetoli, Tanzania, casts doubt thatA. Afarensis made the Laetoli trails. We suggest that another species ofAustralopithecus or an anonymous genus of the Hominidae, with remarkably humanoid feet, walked at Laetoli. It would be imprudent to declare thatHomo was present at Laetoli 3.5 million years ago (my) because there is no evidence of brain expansion, advanced tool manufacture, or other non-locomotor hallmarks of the human condition at Site G.