Multiparameter Assessment of Foam Cell Formation Progression Using a Dual-Color Switchable Fluorescence Probe.

The assessment of atherosclerosis (AS) progression has emerged as a prominent area of research. Monitoring various pathological features of foam cell (FC) formation is imperative to comprehensively assess AS progression. Herein, a simple benzospiropyran-julolidine-based probe, BSJD, with switchable dual-color imaging ability was developed. This probe can dynamically and reversibly adjust its molecular structure and fluorescent properties in different polar and pH environments. Such a polarity and pH dual-responsive characteristic makes it superior to single-responsive probes in dual-color imaging of lipid droplets (LDs) and lysosomes as well as monitoring their interaction. By simultaneously tracking various pathological features, including LD accumulation and size changes, lysosome dysfunction, and dynamically regulated lipophagy, more comprehensive information can be obtained for multiparameter assessment of FC formation progression. Using BSJD, not only the activation of lipophagy in the early stages and inhibition in the later phases during FC formation are clearly observed but also the important roles of lipophagy in regulating lipid metabolism and alleviating FC formation are demonstrated. Furthermore, BSJD is demonstrated to be capable of rapidly imaging FC plaque sites in AS mice with fast pharmacokinetics. Altogether, BSJD holds great promise as a dual-color organelle-imaging tool for investigating disease-related LD and lysosome changes and their interactions.

Thermally activated delayed fluorescence of a Ir(III) complex: absorption and emission properties, nonradiative rates, and mechanism.

One recent experimental study reported a Ir(III) complex with thermally activated delayed fluorescence (TADF) phenomenon in solution, but its luminescent mechanism is elusive. In this work, we combined density functional theory (DFT), time-dependent DFT (TDDFT) and multi-state complete active space second-order perturbation theory (MS-CASPT2) methods to investigate excited-state properties, photophysics, and emission mechanism of this Ir(III) complex. Two main absorption bands observed in experiments can be attributed to the electronic transition from the S0 state to the S1 and S2 states; while, the fluorescence and phosphorescence are generated from the S1 and T1 states, respectively. Both the S1 and T1 states have clear metal-to-ligand charge transfer (MLCT) character. The present computational results reveal a three-state model including the S0, S1 and T1 states to rationalize the TADF behavior. The small energy gap between the S1 and T1 states benefits the forward and reverse intersystem crossing (ISC and rISC) processes. At 300 K, the rISC rate is five orders of magnitude larger than the phosphorescence rate therefore enabling TADF. At 77 K, the rISC rate is sharply decreased but remains close to the phosphorescence rate; therefore, in addition to the phosphorescence, the delayed fluorescence could also contribute to the experimental emission. The estimated TADF lifetime agrees well with experiments, 9.80 vs. 6.67 µs, which further verifies this three-state model.

Combined QM (MS-CASPT2)/MM studies on photocyclization and photoisomerization of a fulgide derivative in toluene solution.

Photocyclization and photoisomerization of fulgides have been extensively studied experimentally and computationally due to their significant potential applications for example as photoswitches in memory devices. However, the reported excited-state decay mechanisms of fulgides do not include the effects of solvation explicitly to date. Herein, calculations using the high-level MS-CASPT2//CASSCF method were conducted to explore the photoinduced excited-state decay processes of the Eα conformer of a fulgide derivative in toluene with solvent effects treated by implicit PCM and explicit QM/MM models, respectively. Several minima and conical intersections were optimized successfully in and between the S0 and S1 states; then, two nonadiabatic excited-state decay channels that could efficiently drive the system to the ground state were proposed based on the excited-state ring-closure and isomerization paths. In addition, we also found that in the ring-closure path, the potential energy surface is essentially barrierless before approaching the conical intersection, while it needs to overcome a small energy barrier along the E → Z photoisomerization path for the nonadiabatic S1 → S0 internal conversion process. The present computational results could provide useful mechanistic insights into the photoinduced cyclization and isomerization reactions of fulgide and its derivatives.

Thermally Activated Delayed Fluorescence Mechanism of a Bicyclic "Carbene-Metal-Amide" Copper Compound: DFT/MRCI Studies and Roles of Excited-State Structure Relaxation.

Herein we investigated the luminescence mechanism of one "carbene-metal-amide" copper compound with thermally activated delayed fluorescence (TADF) using density functional theory (DFT)/multireference configuration interaction, DFT, and time-dependent DFT methods with the polarizable continuum model. The experimentally observed low-energy absorption and emission peaks are assigned to the S1 state, which exhibits clear interligand and partial ligand-to-metal charge-transfer character. Moreover, it was found that a three-state (S0, S1, and T1) model is sufficient to describe the TADF mechanism, and the T2 state should play a negligible role. The calculated S1-T1 energy gap of 0.10 eV and proper spin-orbit couplings facilitate the reverse intersystem crossing (rISC) from T1 to S1. At 298 K, the rISC rate of T1 → S1 (∼106 s-1) is more than 3 orders of magnitude larger than the T1 phosphorescence rate (∼103 s-1), thereby enabling TADF. However, it disappears at 77 K because of a very slow rISC rate (∼101 s-1). The calculated TADF rate, lifetime, and quantum yield agree very well with the experimental data. Methodologically, the present work shows that only considering excited-state information at the Franck-Condon point is insufficient for certain emitting systems and including excited-state structure relaxation is important.

Room-Temperature Phosphorescence and Thermally Activated Delayed Fluorescence in the Pd Complex: Mechanism and Dual Upconversion Channels.

The Pd complex PdN3N exhibits an unusual dual emission of room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF), but the mechanism is elusive. Herein, we employed both density functional theory (DFT) and time-dependent DFT (TD-DFT) methods to explore excited-state properties of this Pd complex, which shows that the S0, S1, T1, and T2 states are involved in the luminescence. Both the S1 → T1 and S1 → T2 intersystem crossing (ISC) processes are more efficient than the S1 fluorescence and insensitive to temperature. However, the direct T1 → S1 and T2-mediated T1 → T2 → S1 reverse ISC (rISC) processes change remarkably with temperature. At 300 K, these two processes are more efficient than the T1 phosphorescence and therefore enable TADF. Importantly, the T1 → S1 rISC and T1 phosphorescence rates are comparable at 300 K, which leads to dual emissions of TADF and RTP, whereas these two channels become blocked at 100 K so that only the T1 phosphorescence is recorded experimentally.

The spin-orbit interaction controls photoinduced interfacial electron transfer in fullerene-perovskite heterojunctions: C60versus C70.

Here, we used collinear and noncollinear density functional theory (DFT) methods to explore the interfacial properties of two heterojunctions between a fullerene (C60 and C70) and the MAPbI3(110) surface. Methodologically, consideration of the spin-orbit interaction has been proven to be required to obtain accurate energy-level alignment and interfacial carrier dynamics between fullerenes and perovskites in hybrid perovskite solar cells including heavy atoms (such as Pb atoms). Both heterojunctions are predicted to be the same type-II heterojunction, but the interfacial electron transfer process from MAPbI3 to C60 is completely distinct from that to C70. In the former, the interfacial electron transfer is slow because of the associated large energy gap, and the excited electrons are thus trapped in MAPbI3 for a while. In contrast, in the latter, the smaller energy gap induces ultrafast electron transfer from MAPbI3 to C70. These points are further supported by DFT-based nonadiabatic dynamics simulations including the spin-orbit coupling (SOC) effects. These gained insights could help rationally design superior fullerene-perovskite interfaces to achieve high power conversion efficiencies of fullerene-perovskite solar cells.

Chemical Bonding as a New Avenue for Controlling Excited-State Properties and Excitation Energy-Transfer Processes in Zinc Phthalocyanine-Fullerene Dyads.

Whether chemical bonding can regulate the excited-state and optoelectronic properties of donor-acceptor dyads has been largely elusive. In this work, we used electronic structure and nonadiabatic dynamics methods to explore the excited-state properties of covalently bonded zinc phthalocyanine (ZnPc)-fullerene (C60 ) dyads with a 6-6 (or 5-6) bonding configuration in which ZnPc is bonded to two carbon atoms shared by the two hexagonal rings (or a pentagonal and a hexagonal ring) in C60 . In both cases, the locally excited (LE) states on ZnPc are spectroscopically bright. However, their different chemical bonding differentiates the electronic interactions between ZnPc and C60 . In the 5-6 bonding configuration, the LE states on ZnPc are much higher in energy than the LE states on C60 . Thus, the excitation energy transfer from ZnPc to C60 is thermodynamically favorable. On the other hand, in the 6-6 bonding configuration, such a process is inhibited because the LE states on ZnPc are the lowest ones. More detailed mechanisms are elucidated from nonadiabatic dynamics simulations. In the 6-6 bonding configuration, no excitation energy transfer was observed. In contrast, in the 5-6 bonding configuration, several LE and charge-transfer (CT) excitons were shown to participate in the energy-transfer process. Further analysis reveals that the photoinduced energy transfer is mediated by a CT exciton, such that electron- and hole-transfer processes take place in a concerted but asynchronous manner in the excitation energy transfer. It is also found that high-level electronic structure methods including exciton effects are indispensable to accurately describe photoinduced energy- and electron-transfer processes. Furthermore, this work opens up new avenues for regulating the excited-state properties of molecular donor-acceptor dyads by means of chemical bonding.

Photoinduced electron transfer from carbon nanotubes to fullerenes: C60versus C70.

Hybrid carbon materials are found to exhibit novel optoelectronic properties at their interfaces, but the related interfacial carrier dynamics is rarely explored theoretically. In this contribution, we have employed density functional theory (DFT) and DFT-based nonadiabatic dynamics methods to explore photoinduced interfacial electron transfer processes at interfaces between a single-walled carbon nanotube with chiral index (6,5) and C60 or C70 (C60@CNT65 and C70@CNT65). We have found that with low E11 excitation, electron transfer takes place from CNT65 to C60 and C70 in both heterojunctions. This process is ultrafast and completed within about 200 fs, which is consistent with recent experiments. Differently, high E22 excitation does not induce electron injection to C60 in C60@CNT65; instead, "hot" electrons produced within CNT65 will be trapped in its higher conduction band for a while because of slow inter-band relaxation. By contrast, in C70@CNT65, high E22 excitation still can lead to ultrafast electron transfer to C70, but only a comparable amount of electrons are transferred (ca. 30%). Interestingly, electrons either remaining on CNT65 or transferred to C70 are trapped in the higher conduction band for a while, similarly, due to slow inter-band relaxation. The present results could be useful to guide the design of excellent interfaces of mixed-dimensional hybrid carbon materials for various optoelectronic applications.

Nonadiabatic Exciton and Charge Separation Dynamics at Interfaces of Zinc Phthalocyanine and Fullerene: Orientation Does Matter.

Interface orientation between zinc phthalocyanine (ZnPc) and fullerene (C60) affects their interfacial charge separation dynamics; however, the underlying physical origin is still elusive. In this work, we have employed the time-dependent density functional theory (TDDFT) method to explore excited-state properties of ZnPc and C60 heterojunctions with both face-on and edge-on configurations. Spectroscopically bright absorption is from locally excited (LE) singlet excitons within ZnPc. In the face-on configuration, LE excitons are much higher in energy than charge-transfer (CT) excitons, thereby making charge separation process favorable. However, in the edge-on configuration, LE excitons are the lowest ones and CT ones are higher in energy; thus, charge separation is not efficient. Subsequently, we have carried out TDDFT-based nonadiabatic dynamics method to simulate photoinduced exciton and charge separation dynamics of ZnPc and C60 heterojunctions with both edge-on and face-on configurations. In the former, there are no exciton transfer and charge separation processes observed within 300 fs simulation time; while, in the latter, fragment-based electronic transition density matrix analysis reveals that only LE excitons |C60ZnPC*⟩ and CT excitons |C60-ZnPC+⟩ are involved. The exciton transfer from |C60ZnPC*⟩ to |C60-ZnPC+⟩ is completed within about 100 fs in which charge separation takes place with electron-hole distances increasing from 1.0 to 4.5 Å. This exciton transfer process is essentially in company with electron transfer from ZnPc to C60 but almost not involving hole transfer. These gained insights not only rationalize experiments but also enrich our knowledge to design donor-acceptor orientations to optimize organic photovoltaic performance.

Stereoselective Excited-State Isomerization and Decay Paths in cis-Cyclobiazobenzene.

Herein, we have employed OM2/MRCI-based full-dimensional nonadiabatic dynamics simulations to explore the photoisomerization and subsequent excited-state decay of a macrocyclic cyclobiazobenzene molecule. Two S1/S0 conical intersection structures are found to be responsible for the excited-state decay. Related to these two conical intersections, we found two stereoselective photoisomerization and excited-state decay pathways, which correspond to the clockwise and counterclockwise rotation motions with respect to the N═N bond of the azo group. In both pathways, the excited-state isomerization is ultrafast and finishes within ca. 69 fs, but the clockwise isomerization channel is much more favorable than the counterclockwise one with a ratio of 74% versus 26%. Importantly, the present work demonstrates that stereoselective pathways exist not only in the photoisomerization of isolated azobenzene (AB)-like systems but also in macrocyclic systems with multiple ABs. This finding could provide useful insights for understanding and controlling the photodynamics of macrocyclic nanostructures with AB units as the main building units.

Transposable elements drive rapid phenotypic variation in Capsella rubella.

Rapid phenotypic changes in traits of adaptive significance are crucial for organisms to thrive in changing environments. How such phenotypic variation is achieved rapidly, despite limited genetic variation in species that experience a genetic bottleneck is unknown. Capsella rubella, an annual and inbreeding forb (Brassicaceae), is a great system for studying this basic question. Its distribution is wider than those of its congeneric species, despite an extreme genetic bottleneck event that severely diminished its genetic variation. Here, we demonstrate that transposable elements (TEs) are an important source of genetic variation that could account for its high phenotypic diversity. TEs are (i) highly enriched in C. rubella compared with its outcrossing sister species Capsella grandiflora, and (ii) 4.2% of polymorphic TEs in C. rubella are associated with variation in the expression levels of their adjacent genes. Furthermore, we show that frequent TE insertions at FLOWERING LOCUS C (FLC) in natural populations of C. rubella could explain 12.5% of the natural variation in flowering time, a key life history trait correlated with fitness and adaptation. In particular, we show that a recent TE insertion at the 3' UTR of FLC affects mRNA stability, which results in reducing its steady-state expression levels, to promote the onset of flowering. Our results highlight that TE insertions can drive rapid phenotypic variation, which could potentially help with adaptation to changing environments in a species with limited standing genetic variation.

A novel berberine-metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats.

In this study, we investigated the biological activities of a novel berberine-metformin hybrid compound (BMH473) as an anti-diabetic agent. BMH473 exhibited significant anti-hyperglycaemic and anti-hyperlipidaemic effects on T2DM rats. In white adipose tissue, BMH473 reduced the perirenal and epididymal adipose tissue mass and modulated the lesions in perirenal adipose tissue, by inhibiting the protein expressions of PPAR-Ɣ, C/EBP-α and SREBP-1c as well as the mRNA expressions of lipogenic genes. Moreover, BMH473 downregulated the levels of pro-inflammatory cytokines in perirenal adipose tissue through the suppression of p-NF-κB. In liver, BMH473 reduced liver ectopic fat accumulation, by regulating the protein expression levels of SREBP-1c and PPAR-α as well as the mRNA expression levels of lipogenic genes. In addition, BMH473 inhibited hepatic gluconeogenesis by promoting the phosphorylation levels of AMPK α and ACC, and down-regulating the mRNA expression levels of FBPase, G6Pase and PEPCK. Furthermore, BMH473 exhibited significant inhibitory effects on lipogenesis and lipid accumulation in 3T3-L1 adipocytes by modulating the protein expression levels of PPAR-Ɣ, C/EBP-α and SREBP-1 c as well as the mRNA expression levels of lipogenic genes. In conclusion, our results suggest that the newly synthesized BMH473 is beneficial for maintaining glucose and lipid homeostasis in type 2 diabetic rats, and exhibits better anti-hyperlipidaemic effects compared to metformin and berberine.

Transposable Elements Contribute to the Adaptation of Arabidopsis thaliana.

Transposable elements (TEs) are mobile genetic elements with very high mutation rates that play important roles in shaping genome architecture and regulating phenotypic variation. However, the extent to which TEs influence the adaptation of organisms in their natural habitats is largely unknown. Here, we scanned 201 representative resequenced genomes from the model plant Arabidopsis thaliana and identified 2,311 polymorphic TEs from noncentromeric regions. We found expansion and contraction of different types of TEs in different A. thaliana populations. More importantly, we identified two TE insertions that are likely candidates to play a role in adaptive evolution. Our results highlight the importance of variations in TEs for the adaptation of plants in general in the context of rapid global climate change.

Nonadiabatic dynamics simulations on internal conversion and intersystem crossing processes in gold(i) compounds.

The position at which the second gold(i)-phosphine group is attached was experimentally found to play a noticeable role in intersystem crossing rates of gold(i) naphthalene derivatives. However, the physical origin is ambiguous. Herein we have employed generalized trajectory-based surface-hopping dynamics simulations to simulate the excited-state relaxation dynamics of these gold(i) naphthalene compounds including both the intersystem crossing process from the initially populated first excited singlet states S1 to triplet manifolds and internal conversion processes within these triplet states. Our predicted intersystem crossing rates are consistent with experiments very well. On the basis of the present results, we have found that (1) ultrafast and subpicosecond intersystem crossing processes are mainly caused by small energy gaps and large spin-orbit couplings between S1 and Tn; (2) adding the second gold(i)-phosphine group does not increase spin-orbit couplings between S1 and Tn but decrease their values remarkably, which implies that heavy-atom effects are state-specific, not state-universal; (3) the position at which the second gold(i)-phosphine group is attached has a remarkable influence on the electronic structures of S1 and Tn and their relative energies, which affect energy gaps and spin-orbit couplings between S1 and Tn and eventually modulate intersystem crossing rates from S1 to Tn. These new insights are very useful for the design of gold-containing compounds with excellent photoluminescence properties. Finally, this work also exemplifies that different isomers of a compound could have distinct excited-state relaxation dynamics.

Adaptation of Arabidopsis thaliana to the Yangtze River basin.

BACKGROUND: Organisms need to adapt to keep pace with a changing environment. Examining recent range expansion aids our understanding of how organisms evolve to overcome environmental constraints. However, how organisms adapt to climate changes is a crucial biological question that is still largely unanswered. The plant Arabidopsis thaliana is an excellent system to study this fundamental question. Its origin is in the Iberian Peninsula and North Africa, but it has spread to the Far East, including the most south-eastern edge of its native habitats, the Yangtze River basin, where the climate is very different. RESULTS: We sequenced 118 A. thaliana strains from the region surrounding the Yangtze River basin. We found that the Yangtze River basin population is a unique population and diverged about 61,409 years ago, with gene flows occurring at two different time points, followed by a population dispersion into the Yangtze River basin in the last few thousands of years. Positive selection analyses revealed that biological regulation processes, such as flowering time, immune and defense response processes could be correlated with the adaptation event. In particular, we found that the flowering time gene SVP has contributed to A. thaliana adaptation to the Yangtze River basin based on genetic mapping. CONCLUSIONS: A. thaliana adapted to the Yangtze River basin habitat by promoting the onset of flowering, a finding that sheds light on how a species can adapt to locales with very different climates.

Long-term balancing selection contributes to adaptation in Arabidopsis and its relatives.

BACKGROUND: In contrast to positive selection, which reduces genetic variation by fixing beneficial alleles, balancing selection maintains genetic variation within a population or species and plays crucial roles in adaptation in diverse organisms. However, which genes, genome-wide, are under balancing selection and the extent to which these genes are involved in adaptation are largely unknown. RESULTS: We performed a genome-wide scan for genes under balancing selection across two plant species, Arabidopsis thaliana and its relative Capsella rubella, which diverged about 8 million generations ago. Among hundreds of genes with shared coding-region polymorphisms, we find evidence for long-term balancing selection in five genes: AT1G35220, AT2G16570, AT4G29360, AT5G38460, and AT5G44000. These genes are involved in the response to biotic and abiotic stress and other fundamental biochemical processes. More intriguingly, for these genes, we detected significant ecological diversification between the two haplotype groups, suggesting that balancing selection has been very important for adaptation. CONCLUSIONS: Our results indicate that beyond the well-known S-locus genes and resistance genes, many loci are under balancing selection. These genes are mostly correlated with resistance to stress or other fundamental functions and likely play a more important role in adaptation to diverse habitats than previously thought.

On the Origin of De Novo Genes in Arabidopsis thaliana Populations.

De novo genes, which originate from ancestral nongenic sequences, are one of the most important sources of protein-coding genes. This origination process is crucial for the adaptation of organisms. However, how de novo genes arise and become fixed in a population or species remains largely unknown. Here, we identified 782 de novo genes from the model plant Arabidopsis thaliana and divided them into three types based on the availability of translational evidence, transcriptional evidence, and neither transcriptional nor translational evidence for their origin. Importantly, by integrating multiple types of omics data, including data from genomes, epigenomes, transcriptomes, and translatomes, we found that epigenetic modifications (DNA methylation and histone modification) play an important role in the origination process of de novo genes. Intriguingly, using the transcriptomes and methylomes from the same population of 84 accessions, we found that de novo genes that are transcribed in approximately half of the total accessions within the population are highly methylated, with lower levels of transcription than those transcribed at other frequencies within the population. We hypothesized that, during the origin of de novo gene alleles, those neutralized to low expression states via DNA methylation have relatively high probabilities of spreading and becoming fixed in a population. Our results highlight the process underlying the origin of de novo genes at the population level, as well as the importance of DNA methylation in this process.

Frequent introgressions from diploid species contribute to the adaptation of the tetraploid Shepherd's purse (Capsella bursa-pastoris).

Adaptation is the most important ability for organisms to survive in diverse habitats. Animals have the option to escape from stressful environments, but plants do not. In plants, polyploids consist of about 30%-70% angiosperms and 95% ferns, of which some are important crops such as cotton and wheat. How polyploid plants adapt to various habitats has been a fundamental question remained largely unanswered. The tetraploid Shepherd's purse (Capsella bursa-pastoris) is one of the most successful plants on earth and has been distributed across the world, thus being an ideal model system for studying the adaptation of polyploids. We found that there are frequent introgressions from congeneric diploids to Shepherd's purse. Ecological niche modeling suggests that ecological differentiation is evident between the introgressed and non-introgressed C. bursa-pastoris, and the introgressions are a source of adaptation. This result links an evolutionary process to the adaptation of polyploids, and sheds light on the breeding strategy of polyploids as well. We conclude that frequent introgressions from congeneric diploids contributed to the acquisition of adequate genetic variations, thereby allowing C. bursa-pastoris to adapt to various habitats across the world. Our results highlight how a polyploid could have successfully established after it originated.

Demographic history and gene flow during silkworm domestication.

BACKGROUND: Gene flow plays an important role in domestication history of domesticated species. However, little is known about the demographic history of domesticated silkworm involving gene flow with its wild relative. RESULTS: In this study, four model-based evolutionary scenarios to describe the demographic history of B. mori were hypothesized. Using Approximate Bayesian Computation method and DNA sequence data from 29 nuclear loci, we found that the gene flow at bottleneck model is the most likely scenario for silkworm domestication. The starting time of silkworm domestication was estimated to be approximate 7,500 years ago; the time of domestication termination was 3,984 years ago. Using coalescent simulation analysis, we also found that bi-directional gene flow occurred during silkworm domestication. CONCLUSIONS: Estimates of silkworm domestication time are nearly consistent with the archeological evidence and our previous results. Importantly, we found that the bi-directional gene flow might occur during silkworm domestication. Our findings add a dimension to highlight the important role of gene flow in domestication of crops and animals.

Pathogen-origin horizontally transferred genes contribute to the evolution of Lepidopteran insects.

BACKGROUND: Horizontal gene transfer (HGT), a source of genetic variation, is generally considered to facilitate hosts' adaptability to environments. However, convincing evidence supporting the significant contribution of the transferred genes to the evolution of metazoan recipients is rare. RESULTS: In this study, based on sequence data accumulated to date, we used a unified method consisting of similarity search and phylogenetic analysis to detect horizontally transferred genes (HTGs) between prokaryotes and five insect species including Drosophila melanogaster, Anopheles gambiae, Bombyx mori, Tribolium castaneum and Apis mellifera. Unexpectedly, the candidate HTGs were not detected in D. melanogaster, An. gambiae and T. castaneum, and 79 genes in Ap. mellifera sieved by the same method were considered as contamination based on other information. Consequently, 14 types of 22 HTGs were detected only in the silkworm. Additionally, 13 types of the detected silkworm HTGs share homologous sequences in species of other Lepidopteran superfamilies, suggesting that the majority of these HTGs were derived from ancient transfer events before the radiation of Ditrysia clade. On the basis of phylogenetic topologies and BLAST search results, donor bacteria of these genes were inferred, respectively. At least half of the predicted donor organisms may be entomopathogenic bacteria. The predicted biochemical functions of these genes include four categories: glycosyl hydrolase family, oxidoreductase family, amino acid metabolism, and others. CONCLUSIONS: The products of HTGs detected in this study may take part in comprehensive physiological metabolism. These genes potentially contributed to functional innovation and adaptability of Lepidopteran hosts in their ancient lineages associated with the diversification of angiosperms. Importantly, our results imply that pathogens may be advantageous to the subsistence and prosperity of hosts through effective HGT events at a large evolutionary scale.