Decoding selectivity: computational insights into AKR1B1 and AKR1B10 inhibition.

Understanding selectivity mechanisms of inhibitors towards highly homologous proteins is of paramount importance in the design of selective candidates. Human aldo-keto reductases (AKRs) pertain to a superfamily of monomeric oxidoreductases, which serve as NADPH-dependent cytosolic enzymes to catalyze the reduction of carbonyl groups to primary and secondary alcohols using electrons from NADPH. Among AKRs, AKR1B1 is emerging as a promising target for cancer treatment and diabetes, despite its high structural similarity with AKR1B10, which leads to severe adverse events. Therefore, it is crucial to understand the selectivity mechanisms of AKR1B1 and AKR1B10 to discover safe anticancer candidates with optimal therapeutic efficacy. In this study, multiple computational strategies, including sequence alignment, structural comparison, Protein Contacts Atlas analysis, molecular docking, molecular dynamics simulation, MM-GBSA calculation, alanine scanning mutagenesis and pharmacophore modeling analysis were employed to comprehensively understand the selectivity mechanisms of AKR1B1/10 inhibition based on selective inhibitor lidorestat and HAHE. This study would provide substantial evidence in the design of potent and highly selective AKR1B1/10 inhibitors in future.

Traffic noise distribution characteristics of high-rise buildings along ultra-wide cross section highway with multiple noise reduction measures.

Nowadays, ultra-wide cross section highway is a hotspot in construction and brings some unique noise distribution characteristics. In this work, we further investigate noise distribution characteristics of diverse building layouts along ultra-wide cross section highway in Guangdong Province with multiple noise mitigation measures. By the aid of vehicle noise emission model and noise mapping, the influence of high-rise building layouts and shielding in the urban planning on noise mitigation is also considered. Some key findings are summarized as follows: (1) Under the same distance, the noise level of non-frontage building facades is higher than frontage building facades. After taking noise reduction measures, the noise reduction effect of non-street-facing building facades, buildings facing the road, and buildings at a long distance to the road is greater than street-facing building facades, buildings sideways to the road, and buildings at a short distance; (2) the distribution trend of insertion loss (IL) of non-frontage buildings is influenced by the height of the frontage buildings. Specifically, the trend of insertion loss first increases and then decreases as the floor rises when the height of non-frontage buildings is higher than frontage buildings. Comparatively, the trend of insertion loss decreases as the floor rises when the height of non-frontage buildings is equal to frontage buildings; (3) when double noise reduction measures are implemented, the noise distribution trend in buildings is similar to that observed with individual noise reduction measure, where the difference between both is only 0.6 dB(A). Thanks to the high representativeness of the case area, this work can provide some design guidance for the urban planning and the selection of noise reduction measures along the ultra-wide cross section highway.

Cloning and functional characterization of a cinnamate 4-hydroxylase gene from the hornwort Anthoceros angustus.

Hornworts, as the sister group to liverworts and mosses, comprise bryophytes, which are critical in understanding the evolution of key land plant traits. Cinnamate 4-hydroxylase (C4H) catalyzes the second step of the phenylpropanoid pathway to synthesize the precursor of numerous phenolic compounds, such as lignin and flavonoids. However, C4H in the hornwort Anthoceros angustus has not yet been cloned and functionally characterized. In this work, we screened the transcriptome database of A. angustus and identified one C4H gene, AnanC4H. AnanC4H maintained conserved cytochrome P450 domains with other typical plant C4Hs. Ultraviolet B irradiation and exogenous application of methyl jasmonate (MeJA) induced the expression of AnanC4H to varying degrees. The coding sequence of AnanC4H was expressed in yeast, and the recombinant proteins were isolated. The recombinant proteins of AnanC4H catalyzed the conversion of trans-cinnamic acid to p-coumaric acid and catalyzed the conversion of 3-hydroxycinnamic acid to caffeic acid. AnanC4H showed higher affinity for trans-cinnamic acid than for 3-hydroxycinnamic acid, but there was no significant difference in the catalytic efficiency of AnanC4H for the two substrates in vitro. Moreover, the expression of AnanC4H in Arabidopsis thaliana led to an increase in both the lignin content and the number of lignified cells in stems. However, there was no significant change in flavonoid content in transgenic Arabidopsis plants.

The response of LncRNAs associated with photosynthesis-and pigment synthesis-related genes to green light in Chlamydomonas reinhardtii.

The quality of light is an important abiotic factor that affects the growth and development of green plants. Ultraviolet, red, blue, and far-red light all have demonstrated roles in regulating green plant growth and development, as well as light morphogenesis. However, the mechanism underlying photosynthetic organism responses to green light throughout the life of them are not clear. In this study, we exposed the unicellular green alga Chlamydomonas reinhardtii to green light and analyzed the dynamics of transcriptome changes. Based on the whole transcriptome data from C. reinhardtii, a total of 9974 differentially expressed genes (DEGs) were identified under green light. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were mainly related to "carboxylic acid metabolic process," "enzyme activity," "carbon metabolism," and "photosynthesis and other processes." At the same time, 253 differentially expressed long non-coding RNAs (DELs) were characterized as green light responsive. We also made a detailed analysis of the responses of photosynthesis- and pigment synthesis-related genes in C. reinhardtii to green light and found that these genes exhibited obvious dynamic expression. Lastly, we constructed a co-expression regulatory network, comprising 49 long non-coding RNAs (lncRNAs) and 20 photosynthesis and pigment related genes, of which 9 mRNAs were also the predicted trans/cis-targets of 8 lncRNAs, these results suggested that lncRNAs may affect the expression of mRNAs related to photosynthesis and pigment synthesis. Our findings give a preliminary explanation of the response mechanism of C. reinhardtii to green light at the transcriptional level.

Telomere-to-telomere and haplotype-resolved genome assembly of the Chinese cork oak (Quercus variabilis).

The Quercus variabilis, a deciduous broadleaved tree species, holds significant ecological and economical value. While a chromosome-level genome for this species has been made available, it remains riddled with unanchored sequences and gaps. In this study, we present a nearly complete comprehensive telomere-to-telomere (T2T) and haplotype-resolved reference genome for Q. variabilis. This was achieved through the integration of ONT ultra-long reads, PacBio HiFi long reads, and Hi-C data. The resultant two haplotype genomes measure 789 Mb and 768 Mb in length, with a contig N50 of 65 Mb and 56 Mb, and were anchored to 12 allelic chromosomes. Within this T2T haplotype-resolved assembly, we predicted 36,830 and 36,370 protein-coding genes, with 95.9% and 96.0% functional annotation for each haplotype genome. The availability of the T2T and haplotype-resolved reference genome lays a solid foundation, not only for illustrating genome structure and functional genomics studies but also to inform and facilitate genetic breeding and improvement of cultivated Quercus species.

Structural and functional properties of different types of siphonous LHCII trimers from an intertidal green alga Bryopsis corticulans.

Light-harvesting complexes of photosystem II (LHCIIs) in green algae and plants are vital antenna apparatus for light harvesting, energy transfer, and photoprotection. Here we determined the structure of a siphonous-type LHCII trimer from the intertidal green alga Bryopsis corticulans by X-ray crystallography and cryo-electron microscopy (cryo-EM), and analyzed its functional properties by spectral analysis. The Bryopsis LHCII (Bry-LHCII) structures in both homotrimeric and heterotrimeric form show that green light-absorbing siphonaxanthin and siphonein occupied the sites of lutein and violaxanthin in plant LHCII, and two extra chlorophylls (Chls) b replaced Chls a. Binding of these pigments expands the blue-green light absorption of B. corticulans in the tidal zone. We observed differences between the Bry-LHCII homotrimer crystal and cryo-EM structures, and also between Bry-LHCII homotrimer and heterotrimer cryo-EM structures. These conformational changes may reflect the flexibility of Bry-LHCII, which may be required to adapt to light fluctuations from tidal rhythms.

Study on the influence of industrial intelligence on carbon emission efficiency-empirical analysis of China's Yangtze River Economic Belt.

How to achieve the goal of "carbon peak and carbon neutrality" and explore the compatibility of industrial and ecological civilization is a major challenge for China today. This study analyzes the impact of industrial intelligence on industrial carbon emissions efficiency in 11 provinces of China's Yangtze River Economic Belt, measuring the efficiency of industrial carbon emissions through the non-expected output slacks-based measure (SBM) model, selecting industrial robot penetration to measure the level of industrial intelligence, establishing a two-way fixed model to verify the impact of industrial intelligence on carbon emission efficiency, and testing for intermediary effects and regional heterogeneity. The results show that: (1) the industrial carbon emission efficiency of the 11 provinces shows year-over-year improvement, with significant differences between upstream, midstream, and downstream, where downstream is the highest and upstream is the lowest. (2) The development of industrial intelligence is highly uneven, with the upstream level being the weakest. (3) Industrial intelligence can improve the efficiency of industrial carbon emissions by enhancing green technological innovation and energy use efficiency. (4) The effect of industrial intelligence on industrial carbon emission efficiency also shows regional heterogeneity. Finally, we present policy recommendations. This research provides mathematical and scientific support for achieving carbon reduction targets at an early stage and helps accelerate the construction of a modern, low-carbon China.

Exploring Applicability of Different Ecological Protection Measures for Soil and Water Loss Control of Highway Slope in the Permafrost Area: A Case Study of Qinghai-Tibet Highway in China.

A variety of slope water and soil conservation measures have been taken along the Qinghai-Tibet Highway, but the systematic comparison of their erosion control ability needs to be strengthened, especially in the permafrost area. To explore the applicability of different measures to control runoff and sediment yield, field scouring experiments were conducted for different ecologically protected slopes, including turfing (strip, block, full), slope covering (gravel, coconut fiber blanket), and comprehensive measures (three-dimensional net seeding). Compared with the bare slope, the bulk density of the plots with the ecological protection measure decreased, the moisture-holding capacity and the organic matter increased correspondingly, and the average runoff velocity also decreased. The soil loss and runoff had a similar trend of different ecological protection measures. The relationship between the cumulative runoff and sediment yield of different measures exhibited a power function, with the increase of scouring flow and the runoff reduction benefit and sediment reduction benefit in different ecological protection-measured plots showing a decreasing trend. The average runoff reduction benefit decreased from 37.06% to 6.34%, and the average sediment reduction benefit decreased from 43.04% to 10.86%. The comprehensive protection measures had the greatest protection efficiency, followed by turfing, while the cover measure had limited improvement. Soil characteristics, vegetation coverage, and the scouring inflow rate are key factors that influence protection efficiency. The results suggest that comprehensive measures and turfing be taken rather than cover measures or bare slopes. This work provides an experimental reference for ecological protection methods for highway slopes in the permafrost area.

Numerical modeling and field test of sonic crystal acoustic barriers.

The rapid development of highway traffic has gradually deteriorated the acoustic environment along the line. Sonic crystal theory provides new ideas for traffic acoustic barrier. However, the lack of practical numerical models and field test verifications has restricted the promotion and application of sonic crystal acoustic barriers (SCABs). In this study, a field test was conducted to study the noise reduction performance of SCAB. The SCAB exhibits excellent wave attenuation in the band gap, when compared with concrete acoustic barriers (CABs) along highways, the noise reduction performance in the band gap is improved by 0.5-2.1 dB(A), especially at the local peak in the highway noise spectrum. However, from the perspective of total insertion loss, CAB performs better than SCAB in all distances in the protected area. Next, the 3D FEM model is established based on the highway site and validated by the measured results. Compared with the commonly used 2D model, the 3D FEM model is more practical for considering the top diffraction and ground reflection, which influence the noise reduction performance a lot and need to be considered. To improve the noise reduction performance of SCAB, three types of optimization measures are explored. The gradient combination of scatterers can effectively improve the noise reduction effect in the low-frequency band gap, especially the high- to low-gradient layout. Besides, not only the porous sound-absorbing material but also the microperforated plates can improve the noise reduction effect, especially outside the band gap. The larger perforation rates and smaller apertures of microperforated plate are preferred in SCAB. This work provides field test support and promotes the application of SCABs in traffic noise control.

Structure of the Acidobacteria homodimeric reaction center bound with cytochrome c.

Photosynthesis converts light energy to chemical energy to fuel life on earth. Light energy is harvested by antenna pigments and transferred to reaction centers (RCs) to drive the electron transfer (ET) reactions. Here, we present cryo-electron microscopy (cryo-EM) structures of two forms of the RC from the microaerophilic Chloracidobacterium thermophilum (CabRC): one containing 10 subunits, including two different cytochromes; and the other possessing two additional subunits, PscB and PscZ. The larger form contained 2 Zn-bacteriochlorophylls, 16 bacteriochlorophylls, 10 chlorophylls, 2 lycopenes, 2 hemes, 3 Fe4S4 clusters, 12 lipids, 2 Ca2+ ions and 6 water molecules, revealing a type I RC with an ET chain involving two hemes and a hybrid antenna containing bacteriochlorophylls and chlorophylls. Our results provide a structural basis for understanding the excitation energy and ET within the CabRC and offer evolutionary insights into the origin and adaptation of photosynthetic RCs.

A chromosome-level genome assembly of the Chinese cork oak (Quercus variabilis).

Quercus variabilis (Fagaceae) is an ecologically and economically important deciduous broadleaved tree species native to and widespread in East Asia. It is a valuable woody species and an indicator of local forest health, and occupies a dominant position in forest ecosystems in East Asia. However, genomic resources from Q. variabilis are still lacking. Here, we present a high-quality Q. variabilis genome generated by PacBio HiFi and Hi-C sequencing. The assembled genome size is 787 Mb, with a contig N50 of 26.04 Mb and scaffold N50 of 64.86 Mb, comprising 12 pseudo-chromosomes. The repetitive sequences constitute 67.6% of the genome, of which the majority are long terminal repeats, accounting for 46.62% of the genome. We used ab initio, RNA sequence-based and homology-based predictions to identify protein-coding genes. A total of 32,466 protein-coding genes were identified, of which 95.11% could be functionally annotated. Evolutionary analysis showed that Q. variabilis was more closely related to Q. suber than to Q. lobata or Q. robur. We found no evidence for species-specific whole genome duplications in Quercus after the species had diverged. This study provides the first genome assembly and the first gene annotation data for Q. variabilis. These resources will inform the design of further breeding strategies, and will be valuable in the study of genome editing and comparative genomics in oak species.

DHW-221, a Dual PI3K/mTOR Inhibitor, Overcomes Multidrug Resistance by Targeting P-Glycoprotein (P-gp/ABCB1) and Akt-Mediated FOXO3a Nuclear Translocation in Non-small Cell Lung Cancer.

Multidrug resistance (MDR) is considered as a primary hindrance for paclitaxel failure in non-small cell lung cancer (NSCLC) patients, in which P-glycoprotein (P-gp) is overexpressed and the PI3K/Akt signaling pathway is dysregulated. Previously, we designed and synthesized DHW-221, a dual PI3K/mTOR inhibitor, which exerts a remarkable antitumor potency in NSCLC cells, but its effects and underlying mechanisms in resistant NSCLC cells remain unknown. Here, we reported for the first time that DHW-221 had favorable antiproliferative activity and suppressed cell migration and invasion in A549/Taxol cells in vitro and in vivo. Importantly, DHW-221 acted as a P-gp inhibitor via binding to P-gp, which resulted in decreased P-gp expression and function. A mechanistic study revealed that the DHW-221-induced FOXO3a nuclear translocation via Akt inhibition was involved in mitochondrial apoptosis and G0/G1 cell cycle arrest only in A549/Taxol cells and not in A549 cells. Interestingly, we observed that high-concentration DHW-221 reinforced the pro-paraptotic effect via stimulating endoplasmic reticulum (ER) stress and the mitogen-activated protein kinase (MAPK) pathway. Additionally, intragastrically administrated DHW-221 generated superior potency without obvious toxicity via FOXO3a nuclear translocation in an orthotopic A549/Taxol tumor mouse model. In conclusion, these results demonstrated that DHW-221, as a novel P-gp inhibitor, represents a prospective therapeutic candidate to overcome MDR in Taxol-resistant NSCLC treatment.

Structural insights into the interactions between lloviu virus VP30 and nucleoprotein.

The family Filoviridae comprises many notorious viruses, such as Ebola virus (EBOV) and Marburg virus (MARV), that can infect humans and nonhuman primates. Lloviu virus (LLOV), a less well studied filovirus, is considered a potential pathogen for humans. The VP30 C-terminal domain (CTD) of these filoviruses exhibits nucleoprotein (NP) binding and plays an essential role in viral transcription, replication and assembly. In this study, we confirmed the interactions between LLOV VP30 CTD and its NP fragment, and also determined the crystal structure of the chimeric dimeric LLOV NP-VP30 CTD at 2.50 Å resolution. The structure is highly conserved across the family Filoviridae. While in the dimer structure, only one VP30 CTD binds the NP fragment, which indicates that the interaction between LLOV VP30 CTD and NP is not strong. Our work provides a preliminary model to investigate the interactions between LLOV VP30 and NP and suggests a potential target for anti-filovirus drug development.

Ligand-binding specificities of four odorant-binding proteins in Conogethes punctiferalis.

Odorant-binding proteins (OBPs) play essential roles in lepidopteran insects' perception of host volatiles by binding and transporting hydrophobic ligands. The yellow peach moth (YPM), Conogethes punctiferalis (Guenée), is a serious agricultural pest, with broad host range and cryptic feeding habits. However, few studies about YPM perceiving pheromones and host plant odorants have been reported. In this study, four OBP genes (CpunOBP8, CpunOBP9, CpunABP, and CpunGOBP2) were cloned from the antennae of YPM. The recombinant proteins were expressed and purified by prokaryotic expression system, with their binding affinities to 26 ligands being tested. Four CpunOBPs all had six conserved cysteine residues, which were typical structural characteristics of classical OBPs. The fluorescence competitive binding assay indicated that CpunOBP8 and CpunABP could not only exhibit high binding affinities to female sex pheromones, but also to host plant odorants. For example, CpunOBP8 bound strongly with cis-10-hexadecenal, hexadecanal, and so forth, whereas CpunABP bound with cis-10-hexadecenal, camphene, and 3-carene. Comparatively, CpunOBP9 and CpunGOBP2 could only bind with host plant odorants, with CpunOBP9 binding strongly to 3-methyl-1-butanol, hexyl acetate, and so forth, while CpunGOBP2 displaying the widest binding spectra and correlating with 3-carene, pentyl acetate, and so forth. The results indicated that on the one hand, each of the four CpunOBPs had its specific binding spectra when binding and transporting olfactory ligands; on the other hand, the same ligand might be bound to more than one CpunOBPs, which would provide information for the potential application of semiochemicals in controlling YPM.

DZW-310, a novel phosphoinositide 3-kinase inhibitor, attenuates the angiogenesis and growth of hepatocellular carcinoma cells via PI3K/AKT/mTOR axis.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide with high lethality and prevalence. The deregulated phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays an indispensable role in mediating the progression of HCC. Among them, PI3K acts as the most pivotal initiator, contributing to multiple malignant biological processes, like proliferation, apoptosis and angiogenesis. Many PI3K inhibitors (PI3Kis) have been proved or proceeded into clinical as antineoplastic drugs. Nevertheless, the application of PI3Kis for the treatment of HCC remains a blank. Accordingly, our study identified a novel PI3Ki (DZW-310) with strong anti-HCC activity in vitro and in vivo. This study aimed to evaluate its anti-HCC effect and elucidate its potential mechanism. Our current results revealed that DZW-310 significantly attenuated HCC cell growth through promoting intrinsic apoptosis and G0/G1 phase cell arrest. Moreover, DZW-310 suppressed angiogenesis by regulating the HIF-1α/VEGFA axis. Further mechanistic investigation demonstrated that DZW-310, functioned as a PI3Ki, exerted strong anti-HCC activity by acting on PI3Kα (a major subtype of PI3K) and ulteriorly deactivating the PI3K/AKT/mTOR pathway. Collectively, our studies identified that DZW-310 is expected to become a promising HCC therapeutic agent and broaden clinical application of PI3Ki in HCC chemotherapy.

Assembly of LHCA5 into PSI blue shifts the far-red fluorescence emission in higher plants.

In higher plants, the PSI core complex is associated with light-harvesting complex I (LHCI), forming the PSI-LHCI super-complex. In vascular plants, four major antenna proteins (LHCA1-4) are assembled in the order of LHCA1, LHCA4, LHCA2, and LHCA3 into a crescent-shaped LHCI, while LHCA5 and LHCA6 are minor antenna proteins. By contrast, in moss and green algae, LHCA5 or LHCA5-like protein functions as one of the major antenna proteins by residing at the second site of LHCI. In order to learn the effect of binding different LHCA proteins, i.e. LHCA4 or LHCA5, within the PSI-LHCI super-complex on photosynthetic properties of plants, we constructed LHCA5 overexpression plants with a wild type (WT) background and an lhca4 mutant background in Arabidopsis thaliana. The results showed that: (i) there are little difference in phenotype, pigment composition and chlorophyll fluorescence parameters between the transgenic Arabidopsis and their corresponding background materials; (ii) in spite of a small amount of LHCA5, the LHCA5-included PSI-LHCI super-complex can be obtained by extracting samples incubated with anti-FLAG M2 Affinity Gel, in which LHCA5 is found to substitute for LHCA4 as analyzed by immunoblotting analysis; (iii) the replacement of LHCA4 with LHCA5 within PSI-LHCI super-complex leads to a blue shift in low temperature fluorescence emission, suggesting a decrease in far-red absorbance. These results provide new clues for understanding the position and function of LHCA4 and LHCA5 during the evolution of green plants from aquatic to terrestrial lifestyles.

Penicillium fungi mediate behavioral responses of the yellow peach moth, Conogethes punctiferalis (Guenée) to apple fruits via altering the emissions of host plant VOCs.

Plant-associated microbes have been reported as important but overlooked drivers of plant-herbivorous insect interactions. Influence of plant-associated microbes on plant-insect interactions is diverse, including beneficial, detrimental, and neutral. Here, we determined the effects of three Penicillium fungi, including Penicillium citrinum, Penicillium sumatrense, and Penicillium digitatum, on the oviposition selection and behavior of the yellow peach moth (YPM), Conogethes punctiferalis (Guenée). Compared with fungi noninfected apples (NIA), mechanically damaged apples (MDA), and P. citrinum in potato dextrose agar medium (PC), the oviposition selection and four-arm olfactometer experiments both showed that mated YPM females preferred to P. citrinum-infected apples (PCA). For P. sumatrense or P. digitatum, we also found that mated YPM females preferred to P. sumatrense-infected apples (PSA) or P. digitatum-infected apples (PDA), respectively. Among three Penicillium fungi-infected apples, the selection rates including oviposition and olfactometer behavior of mated YPM females on PDA were both higher than those on PSA and PCA. Further analyses of host plant volatile organic compounds (VOCs) by GC-MS showed that the absolute contents of ethyl hexanoate and (Z, E)-α-farnesene in PCA, PSA, and PDA were all higher than those in NIA, and a total of 16 novel VOCs were detected in fungi-infected apples (PCA, PSA, and PDA), indicating that fungi infection changed the components and proportions of apple VOCs. Taken together, three Penicillium fungi play significant roles in mediating the host selection of YPMs via altering the emissions of VOCs. These findings will be beneficial for developing formulations for field trapping of YPMs in the future.

ZDQ-0620, a Novel Phosphatidylinositol 3-Kinase Inhibitor, Inhibits Colorectal Carcinoma Cell Proliferation and Suppresses Angiogenesis by Attenuating PI3K/AKT/mTOR Pathway.

The PI3K/AKT pathway plays a central role in human cancers, aberrant activation of this pathway is associated with tumorigenesis, cancer progression and angiogenesis. Based on the importance of the PI3K/AKT pathway in malignancies, we developed a 4-aminoquinazoline derivative, ZDQ-0620, initially envisioned as a novel pan-PI3K inhibitor. This study aimed to evaluate the potential target of ZDQ-0620 and its anticancer effect in human colorectal carcinoma (CRC). PI3K-kinase activity test showed IC50 of ZDQ-0620 against PI3Ka was 0.5 nM; molecular docking, CETSA assay and western blotting was further performed to predict ZDQ-0620 was a PI3K/AKT pathway inhibitor by targeting PI3K. To identify the effect of ZDQ-0620 on CRC cells, Sulforhodamine B (SRB) assay, flow cytometry, and Cell morphology analysis were conducted. The results showed that ZDQ-0620 inhibited the proliferation, migration and invasion of CRC cells, induced apoptosis through G0/G1 cell cycle arrest and mitochondrial pathway. Additionally, ZDQ-0620 inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). In vivo, neovascularization of rat aortic ring and chick chorioallantoic membrane (CAM) induced by VEGF was diminished when treated with ZDQ-0620. These results indicate that ZDQ-0620 induce apoptosis and anti-angiogenesis via inhibits the PI3K/AKT pathway. We suggest that the great potential of ZDQ-0620 as an effective treatment candidate against CRC.

Structural elucidation of vascular plant photosystem I and its functional implications.

In vascular plants, bryophytes and algae, the photosynthetic light reaction takes place in the thylakoid membrane where two transmembrane supercomplexes PSII and PSI work together with cytochrome b 6 f and ATP synthase to harvest the light energy and produce ATP and NADPH. Vascular plant PSI is a 600-kDa protein-pigment supercomplex, the core complex of which is partly surrounded by peripheral light-harvesting complex I (LHCI) that captures sunlight and transfers the excitation energy to the core to be used for charge separation. PSI is unique mainly in absorption of longer-wavelengths than PSII, fast excitation energy transfer including uphill energy transfer, and an extremely high quantum efficiency. From the early 1980s, a lot of effort has been dedicated to structural and functional studies of PSI-LHCI, leading to the current understanding of how more than 200 cofactors are kept at the correct distance and geometry to facilitate fast energy transfer in this supercomplex at an atomic level. In this review, we review the history of studies on vascular plant PSI-LHCI, summarise the present research progress on its structure, and present some new and further questions to be answered in future studies.

LHCA4 residues surrounding red chlorophylls allow for fine-tuning of the spectral region for photosynthesis in Arabidopsis thaliana.

Improving far-red light utilization could be an approach to increasing crop production under suboptimal conditions. In land plants, only a small part of far-red light can be used for photosynthesis, which is captured by the antenna proteins LHCAs of photosystem I (PSI) through the chlorophyll (Chl) pair a603 and a609. However, it is unknown how the energy level of Chls a603-a609 is fine-tuned by the local protein environment in vivo. In this study, we investigated how changing the amino acid ligand for Chl a603 in LHCA4, the most red-shifted LHCA in Arabidopsis thaliana, or one amino acid near Chl a609, affected the energy level of the resulting PSI-LHCI complexes in situ and in vitro. Substitutions of the Chl a603 ligand N99 caused a blue shift in fluorescence emission, whereas the E146Q substitution near Chl a609 expanded the emission range to the red. Purified PSI-LHCI complexes with N99 substitutions exhibited the same fluorescence emission maxima as their respective transgenic lines, while the extent of red shift in purified PSI-LHCI with the E146Q substitution was weaker than in the corresponding transgenic lines. We propose that substituting amino acids surrounding red Chls can tune their energy level higher or lower in vivo, while shifting the absorption spectrum more to the red could prove more difficult than shifting to the blue end of the spectrum. Here, we report the first in vivo exploration of changing the local protein environment on the energy level of the red Chls, providing new clues for engineering red/blue-shifted crops.