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Molecular oxygen activation often suffers from high energy consumption and low efficiency. Developing eco-friendly and effective photocatalysts remains a key challenge for advancing green molecular oxygen activation. Herein, graphitic carbon nitride (g-C 3 N 4 ) with abundant hydroxyl groups (HCN) was synthesized to investigate the relationship between these polar groups and molecular oxygen activation. The advantage of the hydroxyl group modification of g-C 3 N 4 included narrower interlayer distances, a larger specific surface area and improved hydrophilicity. Various photoelectronic measurements revealed that the introduced hydroxyl groups reduced the charge transfer resistance of HCN, resulting in accelerated charge separation and migration kinetics. Therefore, the optimal HCN-90 showed the highest activity for Rhodamine B photodegradation with a reaction time of 30 min and an apparent rate constant of 0.125 min -1 , surpassing most other g-C 3 N 4 composites. This enhanced activity was attributed to the adjusted band structure achieved through polar functional group modification. The modification of polar functional groups could alter the energy band structure of photocatalysts, narrow band gap, enhance visible-light absorption, and improve photogenerated carrier separation efficiency. This work highlights the significant potential of polar functional groups in tuning the structure of g-C 3 N 4 to enhance efficient molecular oxygen activation.

Chiroptical nanomaterials with circularly polarized luminescence (CPL) performance have aroused increasing attention. Herein, multicolor CPL-active Janus nanofibers are prepared through a simple parallel electrospinning method using chiral helical polyacetylenes as the chiral source and achiral fluorophores as the fluorescent source. Interestingly, despite a direct spatial isolation between the chiral component and the fluorescent component, blue and green CPL emissions can still be obtained due to the fluorescence-selective absorption behavior of chiral helical polyacetylenes, with a satisfactory dissymmetric factor ( g lum ) of 2 × 10 -2 and 2.5 × 10 -3 , respectively. Moreover, by taking advantage of the circular polarization fluorescence energy transfer process, red CPL emission is further achieved using the obtained blue and green CPL as energy donors and the achiral red fluorophore as an energy acceptor. The present work offers a facile approach to prepare multilevel-structured chiroptical materials with promising application potentials in a flexible photoelectric device.

Mucin-related tumor-associated carbohydrate antigens (TACAs) are important and interesting targets for cancer vaccine therapy. However, efficient access to a library of mucin-related TACAs remains a challenging task. One of the key issues is the challenging construction of α-GalNAc linkages. Here, we report highly stereoselective α-glycosylation with GalN 3 N -phenyl trifluoroacetimidate donors, which features excellent yields, outstanding stereoselectivities, broad substrate scope and mild reaction conditions. This method is successfully applied to highly stereoselective synthesis of GalN 3 -α- O -Ser, which served as the common intermediate for collective synthesis of a wide range of TACAs including T N antigen, ST N antigen, 2,6 STF antigen, 2,3 STF antigen, glycophorin and cores 1-8 mucin-type O -glycans. In particular, the rationale for this highly stereoselective α-glycosylation is provided for the first time using DFT calculations and mechanistic studies, highlighting the crucial roles of reagent combinations (TMSI and Ph 3 PO) and the H-bonding directing effect of the N 3 group., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Background: Therapy-related acute myeloid leukemia (t-AML) is considered high risk as it related to prior exposure to cytotoxic chemotherapy agents for solid tumors or hematologic malignancies. Compared with de novo AML, t-AML is associated with lower remission rates, inferior overall survival (OS) and higher relapse rates. Many efforts have been devoted to improving the overall but with limited success, and novel strategy is thus highly needed., Case Description: We reported one patient with refractory/relapsed t-AML was successfully treated with Palbociclib combined with Venetoclax and Azacytidine (AZA). In this case, a 47-year-old patient with t-AML recurred during Venetoclax in combination with AZA therapy. However, the patient achieved morphological, immunophenotypic and molecular complete remission again after Palbociclib combined with Venetoclax and AZA., Conclusions: Although only one successful case is presented here, three-drug combination regimens should be considered as another treatment option for t-AML in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The p38 mitogen-activated protein kinases (MAPKs) are associated with insect immunity, tissue repair, and the insecticidal activity of Bacillus thuringiensis (Bt). Here, a p38 MAPK family gene ( Sep38 β) was identified from Spodoptera exigua . Among the developmental stages, the transcription level of Sep38 β was the highest in egg, followed by that in prepupa and pupa. Sep38 β expression peaked in Malpighian tubules and the hemolymph of fifth instar larvae. Knockdown of Sep38 β or injection of SB203580 (a p38 MAPK inhibitor) significantly downregulated the SeDUOX expression and reactive oxygen species (ROS) level in the midgut, accounting for deterioration of the midgut to scavenge pathogens and enhancement of Bt insecticidal activity. In conclusion, all the results demonstrate that Sep38 β regulates the immune-related ROS level in the insect midgut, which suppresses the insecticidal activity of Bt against S. exigua by 17-22%. Our study highlights that Sep38 β is essential for insect immunity and the insecticidal activity of Bt to S. exigua and is a potential target for pest control.

Ore resources in the mining process form a large number of unmanageable tailings, mostly inhalable fine mineral particles, into the environment will cause serious pollution, and recycling is a precious resource. The cyclone classification provides the possibility for the recovery and exploitation of fine particles, but the recovery and utilization rate of conventional cyclone separation is seriously low, and the performance urgently should be optimized. In the present study, a new type of volute feed was proposed to strengthen the classification and recovery process of fine mineral particles. Combined with numerical simulation and experimental research, the effects of various structural parameters and operating parameters on the flow field distribution, particle motion, and classification performance were systematically examined. The obtained results reveal that the new volute feed structure can effectively reduce the internal turbulence and improve the flow field stability and particle classification efficiency. Compared with the traditional hydrocyclone, the classification efficiency of fine particles with new feed structure increases by 10-18%. Increasing underflow diameter and feed pressure and reducing overflow diameter and feed concentration are also beneficial to lessening classification particle size and enhancing classification performance. The currently achieved outcomes can provide valuable guidelines for further development of novel hydrocyclones., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands 1-6 . The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gα q and the arrestin-biased ligand SBI-553 7 . The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Gα q protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Five ester-bonded gemini quaternary ammonium surfactants C 12 -E n -C 12 (n = 2, 4, 6), with a flexible spacer group, and C 12 -B m -C 12 (m = 1, 2), with rigid benzene spacers, were synthesized via a two-step reaction and analyzed. Furthermore, the effects of the spacer structure, spacer length and polymerization degree on the self-aggregation, antimicrobial activity and cytotoxicity of C 12 -E n -C 12 and C 12 -B m -C 12 and their corresponding monomer N -dodecyl- N , N , N -trimethyl ammonium chloride DTAC were investigated. The results showed that C 12 -E n -C 12 and C 12 -B m -C 12 had markedly lower critical micellar concentration (CMC) values and lower surface tension than DTAC. Moreover, the CMC values of C 12 -E n -C 12 and C 12 -B m -C 12 decreased with increasing spacer length. In the case of equivalent chain length, the rigidity and steric hindrance of phenylene and 1,4-benzenediyl resulted in larger CMC values for C 12 -B m -C 12 than for C 12 -E n -C 12 . The antibacterial ability of C 12 -E n -C 12 and C 12 -B m -C 12 was assessed using Escherichia coli ( E. coli ) and Staphylococcus albus ( S. aureus ) based on minimum inhibitory concentrations (MICs). Furthermore, C 12 -E n -C 12 and C 12 -B m -C 12 exhibited higher antimicrobial activity than DTAC and had stronger function toward S. aureus than E. coli . The antimicrobial activity was enhanced by increasing the spacer chain length and decreased with the increased rigidity of the spacers. The cytotoxic effects of C 12 -E n -C 12 and C 12 -B m -C 12 in cultured Hela cells were evaluated by the standard CCK8 method based on half-maximal inhibitory concentration (IC 50 ). The cytotoxicity of C 12 -E n -C 12 and C 12 -B m -C 12 was significantly lower than alkanediyl-α,ω-bis(dimethyldodecylammonium) bromide surfactants and DTAC. The spacer structure and the spacer length could induce significant cytotoxic effects on Hela cells. These findings indicate that the five ester-bonded GQASs have stronger antibacterial activity and lower toxicity profile, and thus can be used in the pharmaceutical industry.

The gut microbiota is essential for the growth and development of insects, and the intestinal immune system plays a critical role in regulating the homeostasis of intestinal microorganisms and their interactions with pathogenic bacteria. Infection with Bacillus thuringiensis (Bt) can disrupt the gut microbiota of insects, but the regulatory factors governing the interaction between Bt and gut bacteria are not well understood. Uracil secreted by exogenous pathogenic bacteria can activate DUOX-mediated reactive oxygen species (ROS) production, which helps maintain intestinal microbial homeostasis and immune balance. To elucidate the regulatory genes involved in the interaction between Bt and gut microbiota, we investigate the effects of uracil derived from Bt on gut microbiota, and host immunity using a uracil deficient Bt strain (Bt GS57△ pyrE ) obtained by homologous recombination. We analyze the biological characteristics of the uracil deficient strain and found that the deletion of uracil in Bt GS57 strain changed the diversity of gut bacteria in Spodoptera exigua , as investigated using Illumina HiSeq sequencing. Furthermore, qRT-PCR analysis showed that compared with Bt GS57 (control), the expression of the SeDuox gene and the level of ROS were significantly decreased after feeding with Bt GS57△ pyrE . Adding uracil to Bt GS57△ pyrE restored the expression level of DUOX and ROS to a higher level. Additionally, we observed that PGRP-SA , attacin, defensin and ceropin genes were significant different in the midgut of S. exigua infected by Bt GS57 and Bt GS57△ pyrE , with a trend of increasing first and then decreasing. These results suggest that uracil regulates and activates the DUOX-ROS system, affects the expression of antimicrobial peptide genes, and disturb intestinal microbial homeostasis. We preliminarily speculate that uracil is a key factor in the interaction between Bt and gut microbiota, and these findings provide a theoretical basis for clarifying the interaction between Bt, host, and intestinal microorganisms, as well as for gaining new insights into the insecticidal mechanism of B. thuringiensis in insects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wu, Li, Wang, Ji, Guo and Guo.)

Objectives: Our objective was to develop and implement a system to solve the problems that students have as a result of few opportunities for consultation and hands-on exercise in nursing practice teaching, including an inability to participate in the whole process of patients' treatment and nursing, and lack of humanistic care for patients. Methods: The application of the system was conducted among undergraduate nursing students. In 2020, we cooperated with companies and jointly developed a virtual reality (VR) simulation of rehabilitation nursing for patients with cervical spondylosis (CS) and applied it to undergraduate nursing students. Results: The cumulative online training time of 79 students was (30.52±16.28) minutes/person and the average number of learning times was (3.12±1.78) times/person. Overall, 97.5% of the students rated the system as excellent. Conclusions: In thi s paper, we introduce the design, system construction, teaching design, and preliminary application effects of the system. In addition, we discuss the advantages, characteristics, limitations and countermeasures of the system, to provide reference for the construction of VR simulation experimental teaching courses for undergraduate nursing students under the background of new medical science.

Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ET A R) and B (ET B R). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ET A R and ET B R bound to ET-1 and ET B R bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes., (© 2023. The Author(s).)

Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes infertility and ovarian hyperstimulation syndrome. Here we report cryo-EM structures of FSHR in both inactive and active states, with the active structure bound to FSH and an allosteric agonist compound 21 f. The structures of FSHR are similar to other glycoprotein hormone receptors, highlighting a conserved activation mechanism of hormone-induced receptor activation. Compound 21 f formed extensive interactions with the TMD to directly activate FSHR. Importantly, the unique residue H615 7.42 in FSHR plays an essential role in determining FSHR selectivity for various allosteric agonists. Together, our structures provide a molecular basis of FSH and small allosteric agonist-mediated FSHR activation, which could inspire the design of FSHR-targeted drugs for the treatment of infertility and controlled ovarian stimulation for in vitro fertilization., (© 2023. The Author(s).)

Endogenous ions play important roles in the function and pharmacology of G protein-coupled receptors (GPCRs) with limited atomic evidence. In addition, compared with G protein subtypes G s , G i/o , and G q/11 , insufficient structural evidence is accessible to understand the coupling mechanism of G 12/13 protein by GPCRs. Orphan receptor GPR35, which is predominantly expressed in the gastrointestinal tract and is closely related to inflammatory bowel diseases (IBDs), stands out as a prototypical receptor for investigating ionic modulation and G 13 coupling. Here we report a cryo-electron microscopy structure of G 13 -coupled GPR35 bound to an anti-allergic drug, lodoxamide. This structure reveals a novel divalent cation coordination site and a unique ionic regulatory mode of GPR35 and also presents a highly positively charged binding pocket and the complementary electrostatic ligand recognition mode, which explain the promiscuity of acidic ligand binding by GPR35. Structural comparison of the GPR35-G 13 complex with other G protein subtypes-coupled GPCRs reveals a notable movement of the C-terminus of α5 helix of the Gα 13 subunit towards the receptor core and the least outward displacement of the cytoplasmic end of GPR35 TM6. A featured 'methionine pocket' contributes to the G 13 coupling by GPR35. Together, our findings provide a structural basis for divalent cation modulation, ligand recognition, and subsequent G 13 protein coupling of GPR35 and offer a new opportunity for designing GPR35-targeted drugs for the treatment of IBDs., (© 2022. The Author(s).)

Introduction: Wuxi dialect is a variation of Wu dialect spoken in eastern China and is characterized by a rich tonal system. Compared with standard Mandarin speakers, those of Wuxi dialect as their mother tongue can be more efficient in varying vocal cues to encode communicative meanings in speech communication. While literature has demonstrated that speakers encode high vs. low confidence in global prosodic cues at the sentence level, it is unknown how speakers' intended confidence is encoded at a more local, phonetic level. This study aimed to explore the effects of speakers' intended confidence on both prosodic and formant features of vowels in two lexical tones (the flat tone and the contour tone) of Wuxi dialect., Methods: Words of a single vowel were spoken in confident, unconfident, or neutral tone of voice by native Wuxi dialect speakers using a standard elicitation procedure. Linear-mixed effects modeling and parametric bootstrapping testing were performed., Results: The results showed that (1) the speakers raised both F1 and F2 in the confident level (compared with the neutral-intending expression). Additionally, F1 can distinguish between the confident and unconfident expressions; (2) Compared with the neutral-intending expression, the speakers raised mean f0, had a greater variation of f0 and prolonged pronunciation time in the unconfident level while they raised mean intensity, had a greater variation of intensity and prolonged pronunciation time in the confident level. (3) The speakers modulated mean f0 and mean intensity to a larger extent on the flat tone than the contour tone to differentiate between levels of confidence in the voice, while they modulated f0 and intensity range more only on the contour tone., Discussion: These findings shed new light on the mechanisms of segmental and suprasegmental encoding of speaker confidence and lack of confidence at the vowel level, highlighting the interplay of lexical tone and vocal expression in speech communication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ji, Hu and Jiang.)

Luteinizing hormone-choriogonadotropin receptor (LHCGR), a class A G protein-coupled receptor (GPCR), plays a pivotal role in the maturation of reproductive organs and embryonic development. Compared with other GPCRs, the subfamily of LHCGR has a large extracellular domain (ECD) to interact with glycoprotein hormones. A unique hinge region connects the ECD and transmembrane domain (TMD) to transfer the activation signal. However, the signal transmission mechanism remains largely unknown. Here, both molecular dynamics simulation and evolutional analysis were applied to explore the effect of the hinge region on signal transmission. The glycoprotein hormone determined specific hinge region conformations, including the position of a long hinge loop and the ECD-TMD interface. With the hormone, the hinge region showed a characteristic rotation and displayed an active-like conformational landscape of the ECD-TMD interface with an extended TMD. The active-like hinge region conformation transduces the hormone binding signal downwards from ECD to TMD. The relationship between the hinge region and the intracelluar G protein-binding pocket was also inferred. The hinge region-mediated signal transmission mechanism offers a deeper understanding of LHCGR and provides insights into the elucidation of GPCR activation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Thyroid-stimulating hormone (TSH), through activation of its G-protein-coupled thyrotropin receptor (TSHR), controls the synthesis of thyroid hormone-an essential metabolic hormone 1-3 . Aberrant signalling of TSHR by autoantibodies causes Graves' disease (hyperthyroidism) and hypothyroidism, both of which affect millions of patients worldwide 4 . Here we report the active structures of TSHR with TSH and the activating autoantibody M22 5 , both bound to the allosteric agonist ML-109 6 , as well as an inactivated TSHR structure with the inhibitory antibody K1-70 7 . Both TSH and M22 push the extracellular domain (ECD) of TSHR into an upright active conformation. By contrast, K1-70 blocks TSH binding and cannot push the ECD into the upright conformation. Comparisons of the active and inactivated structures of TSHR with those of the luteinizing hormone/choriogonadotropin receptor (LHCGR) reveal a universal activation mechanism of glycoprotein hormone receptors, in which a conserved ten-residue fragment (P10) from the hinge C-terminal loop mediates ECD interactions with the TSHR transmembrane domain 8 . One notable feature is that there are more than 15 cholesterols surrounding TSHR, supporting its preferential location in lipid rafts 9 . These structures also highlight a similar ECD-push mechanism for TSH and autoantibody M22 to activate TSHR, therefore providing the molecular basis for Graves' disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

MicroRNAs (miRNAs) play a pivotal role in regulating a number of physiologic and pathologic processes including bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, making them a candidate used to promote osteogenesis. However, due to intrinsic structure and characteristics, "naked" miRNAs are unstable in serum and could not pass across the cellular membrane. Nano delivery systems seem to be a solution to these issues. Recently, graphene oxide (GO)-based nanomaterials are considered to be promising for gene delivery due to their unique physiochemical characteristics such as high surface area, biocompatibility, and easy modification. In this work, a GO-based nanocomplex functionalized by polyethyleneglycol (PEG) and polyethylenimine (PEI) was prepared for loading and delivering miR-29b, which participates in multiple steps of bone formation. The nanocomplex revealed good biocompatibility, miRNA loading capacity, and transfection efficiency. The miR-29b/GO-PEG-PEI nanocomplex was capsulated into chitosan (CS) hydrogel for osteogenesis. In vitro and in vivo evaluation indicated that miR-29b/GO-PEG-PEI@CS composite hydrogel was able to promote BMSC osteogenic differentiation and bone regeneration. All these results indicate that PEG/PEI functionalized GO could serve as a promising candidate for miRNA cellular delivery, and the miR-29b/GO-PEG-PEI@CS hydrogel has the potential for repairing bone defects in vivo ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Ji, Li, Xu, Zhang, Zhong, Xu, Yin and Song.)

The Beet armyworm Spodoptera exigua (Lepidoptera: Noctuidae, Spodoptera) is an important global polyphagous pest. Pathogen infection could destroy the intestinal microbial homeostasis of insects, leading to the death of the host. However, the effect of the host intestinal microbial community on the insecticidal effect of Bacillus thuringiensis is rarely studied. In this study, the genome characteristics of Bt GS57 and the diversity and functions of the gut bacteria in S. exigua are investigated using crystal morphology, biological activity, and Illumina HiSeq high-throughput sequencing. The total size of the Bt GS57 genome is 6.17 Mbp with an average G + C content of 35.66%. Furthermore, the Bt GS57 genome contains six cry genes: cry1Ca , cry1Da , cry2Ab , cry9Ea , cry1Ia , and cry1Aa , and a vegetative insecticidal protein gene vip3Aa . The Bt GS57 strain can produce biconical crystals, mainly expressing 70 kDa and 130 kDa crystal proteins. The LC 50 value of the Bt GS57 strain against the S. exigua larvae was 0.339 mg mL -1 . Physiological and biochemical reactions showed that Bt GS57 belongs to B.t. var. thuringiensis . In addition, we found that B. thuringiensis can cause a dynamic change in the gut microbiota of S. exigua , with a significant reduction in bacterial diversity and a substantial increase in bacterial load. In turn, loss of gut microbiota significantly decreased the B. thuringiensis susceptibility of S. exigua larvae. Our findings reveal the vital contribution of the gut microbiota in B. thuringiensis -killing activity, providing new insights into the mechanisms of B. thuringiensis pathogenesis in insects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhao, Wu, Ji, Liu, Guo, Guo and Bi.)

Peptide hormones and neuropeptides are complex signaling molecules that predominately function through G protein-coupled receptors (GPCRs). Two unanswered questions remaining in the field of peptide-GPCR signaling systems pertain to the basis for the diverse binding modes of peptide ligands and the specificity of G protein coupling. Here, we report the structures of a neuropeptide, galanin, bound to its receptors, GAL1R and GAL2R, in complex with their primary G protein subtypes G i and G q , respectively. The structures reveal a unique binding pose of galanin, which almost 'lays flat' on the top of the receptor transmembrane domain pocket in an α-helical conformation, and acts as an 'allosteric-like' agonist via a distinct signal transduction cascade. The structures also uncover the important features of intracellular loop 2 (ICL2) that mediate specific interactions with G q , thus determining the selective coupling of G q to GAL2R. ICL2 replacement in G i -coupled GAL1R, μOR, 5-HT 1A R, and G s -coupled β 2 AR and D1R with that of GAL2R promotes G q coupling of these receptors, highlighting the dominant roles of ICL2 in G q selectivity. Together our results provide insights into peptide ligand recognition and allosteric activation of galanin receptors and uncover a general structural element for G q coupling selectivity., (© 2022. The Author(s).)

In the work, the non-woven cellulose acetate (CA) nanofiber mats were prepared via electrospinning, and CA nanofiber were incorporated into the core layer of the high-pressure laminates (HPLs). When the concentration of CA was 16 wt%, SEM images demonstrated that the morphology of the CA nanofiber mat was the best, with an average diameter of 654±246 nm. When CA nanofiber mats were incorporated into the core layer of HPLs, the mechanical properties of the resulted HPLs composites were significantly improved. Specifically, the tensile strength and elongation at break of the nanofiber mats reinforced HPLs composites increased remarkably to 40.8 ±1.1 MPa and 27.9 ± 0.9 %, respectively, which were nearly 6 times and 4.4 times higher than those of the pure HPLs. Furthermore, the incorporation of the CA nanofiber mats also significantly improved the flame retardancy of the HPLs, which was revealed from the thermogravimetric analysis (TGA) results., (Copyright © 2020. Published by Elsevier Ltd.)

The influenza B virus (IBV) causes seasonal influenza and has accounted for an increasing proportion of influenza outbreaks. IBV mainly causes human infections and has not been found to spread in poultry. The replication mechanism and the determinants of interspecies transmission of IBV are largely unknown. In this study, we found that the host ANP32 proteins are required for the function of the IBV polymerase. Human ANP32A/B strongly supports IBV replication, while ANP32E has a limited role. Unlike human ANP32A/B, chicken ANP32A has low support activity to IBV polymerase because of a unique 33-amino-acid insert, which, in contrast, exhibits species specific support to avian influenza A virus (IAV) replication. Chicken ANP32B and ANP32E have even lower activity compared with human ANP32B/E due to specific amino acid substitutions at sites 129-130. We further revealed that the sites 129-130 affect the binding ability of ANP32B/E to IBV polymerase, while the 33-amino-acid insert of chicken ANP32A reduces its binding stability and affinity. Taken together, the features of avian ANP32 proteins limited their abilities to support IBV polymerase, which could prevent efficient replication of IBV in chicken cells. Our results illustrate roles of ANP32 proteins in supporting IBV replication and may help to understand the ineffective replication of IBV in birds., Competing Interests: The authors have declared that no competing interests exist.

DEXD/H box helicase 60 (DDX60) is a new type of DEAD-box RNA helicase, which is induced to express after virus infection. It might involve in antiviral immunity by promoting RIG-I-like receptor-mediated signal transduction. In addition, previous studies had shown that the expression of DDX60 is related to cancer, but there was still a lack of relevant research in breast cancer. In this study, we used the information of patients with breast cancer in the TCGA database for statistical analysis and found that the breast cancer patients with low expression of DDX60 exhibited radiosensitivity. Comparing the radiotherapy groups with the nonradiotherapy groups, for patients with low expression of DDX60, the adjusted hazard ratio (HR) values for radiotherapy were 0.244 (0.064-0.921) and 0.199 (0.062-0.646) in the training and validation datasets, with the p values 0.040 and 0.007, respectively. However, for patients with high expression of DDX60, the adjusted hazard ratio (HR) values were 3.582 (0.627-20.467) and 2.421 (0.460-12.773), with the p values 0.054 and 0.297, respectively. These results suggested that the expression of DDX60 might strongly associate with individualized radiosensitivity in patients with breast cancer., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Dongrun Xin et al.)

A hyaluronic acid-containing ethosomes (HA-ES) as the transdermal drug delivery system was prepared in this work, and rhodamine B (RB) was used as a model drug to be encapsulated. The obtained HA-ES-RB was then characterized by the surface morphology, entrapment efficiency, drug loading and the stability. Results showed that the prepared HA-ES-RB was spherical and showed good dispersion as well as the stability, with a particle size of below 100 nm. The skin permeation experiments were carried out in vitro with the Franz diffusion cells and the rat dorsal skins were used. It was found that the penetration effect of HA-ES-RB was much better than that of ES-RB. The fluorescence microscopy image showed that HA-ES-RB penetrated into the deepest dermis. The excellent transdermic drug delivery effect of HA-ES-RB maybe attributed from its smaller size, hydration of hyaluronic acid as well as greater potential targeting to skin and skin appendages of liposomal carriers. Moreover, the HA-ES delivery system showed non-cytotoxicity to normal cells, indicating a good biocompatibility. This work provded a hyaluronic acid-containing ethosomes which can offer a quick, high efficient, safe and self-administered transdermal drug delivery system., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Asymmetric somatic hybridization is an efficient crop breeding approach by introducing several exogenous chromatin fragments, which leads to genomic shock and therefore induces genome-wide genetic variation. However, the fundamental question concerning the genetic variation such as whether it occurs randomly and suffers from selection pressure remains unknown., Results: Here, we explored this issue by comparing expressed sequence tags of a common wheat cultivar and its asymmetric somatic hybrid line. Both nucleotide substitutions and indels (insertions and deletions) had lower frequencies in coding sequences than in un-translated regions. The frequencies of nucleotide substitutions and indels were both comparable between chromosomes with and without introgressed fragments. Nucleotide substitutions distributed unevenly and were preferential to indel-flanking sequences, and the frequency of nucleotide substitutions at 5'-flanking sequences of indels was obviously higher in chromosomes with introgressed fragments than in those without exogenous fragment. Nucleotide substitutions and indels both had various frequencies among seven groups of allelic chromosomes, and the frequencies of nucleotide substitutions were strongly negatively correlative to those of indels. Among three sets of genomes, the frequencies of nucleotide substitutions and indels were both heterogeneous, and the frequencies of nucleotide substitutions exhibited drastically positive correlation to those of indels., Conclusions: Our work demonstrates that the genetic variation induced by asymmetric somatic hybridization is attributed to both whole genomic shock and local chromosomal shock, which is a predetermined and non-random genetic event being closely associated with selection pressure. Asymmetric somatic hybrids provide a worthwhile model to further investigate the nature of genomic shock induced genetic variation.

Treatment of hepatocellular carcinoma (HCC) requires sustained suppression of tumor cell growth and metastasis for long-term efficacy. However, traditional intratumoral drug delivery system always exhibits burst release with less therapeutic outcomes. Here, a new self-assembling amphiphilic peptide drug conjugate (SAAPDC) is fabricated as a "two-in-one" nanofiber system comprising a hexapeptide as a matrix metalloproteinases (MMP) inhibitor and doxorubicin (DOX) for the treatment of HCC. The results indicate that doxorubicin-conjugated peptide (DOX-KGFRWR) self-assembles to form long nanofibers showing sustained release property for inhibiting the enzymatic activities of MMP-2 and MMP-9. This nanofiber not only inhibits tumor growth in situ but also effectively prevents pulmonary metastasis in an SMMC7721 cell line-based mouse model. In summary, this hexapeptide-based supermolecule system represents a promising nanoscale platform to sustain drug release with high loading capacity for intratumoral administration. Moreover, the delivery of chemotherapeutic drugs via drug-bearing supramolecular MMP inhibitor nanofibers simultaneously inhibits metastasis and tumor growth to achieve synergistic effects for metastatic HCC therapy.

Peptide-drug conjugates (PDCs) as self-assembly prodrugs have the unique and specific features to build one-component nanomedicines. Supramolecular structure based on PDCs could form various morphologies ranging from nanotube, nanofibre, nanobelt to hydrogel. However, the assembly process of PDCs is too complex to predict or control. Herein, we investigated the effects of extrinsic factors on assembly morphology and the possible formation of nanostructures based on PDCs. To this end, we designed a PDC consisting of hydrophobic drug ( S )-ketoprofen (Ket) and valine-glutamic acid dimeric repeats peptide (L-VEVE) to study their assembly behaviour. Our results showed that the critical assembly concentration of Ket-L-VEVE was 0.32 mM in water to form various nanostructures which experienced from micelle, nanorod, nanofibre to nanoribbon. The morphology was influenced by multiple factors including molecular design, assembly time, pH and hydrogen bond inhibitor. On the basis of experimental results, we speculated the possible assembly mechanism of Ket-L-VEVE. The π-π stacking interaction between Ket molecules could serve as an anchor, and hydrogen bonded-induced β-sheets and hydrophilic/hydrophobic balance between L-VEVE peptide play structure-directing role in forming filament-like or nanoribbon morphology. This work provides a new sight to rationally design and precisely control the nanostructure of PDCs based on aromatic fragment., Competing Interests: We declare we have no competing interests.

In order to prolong NO release and enhance the antibacterial effect, N-Carboxy propionyl chitosan sodium (CPCS) was cross-linked to branched polyethylenimine (bPEI) (CPCS-bPEI) and used as a NO donor. The CPCS-bPEI has been successfully synthesized at different molar ratios of CPCS to bPEI, followed with the reaction with NO gas under a parr high-pressure reactor to yield CPCS-bPEI-NO. Successful preparation of CPCS-bPEI-NO was confirmed by elemental analysis, FITR and SEM. The effective release of NO was determined by in vitro release. The antibacterial assay showed that CPCS-bPEI-NO can effectively inhibit Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). We found that the NO loading amount and antibacterial effect can be adjusted by the molar ratio of CPCS to bPEI, and there was no significant toxicity of CPCS-bPEI-NO, suggesting that it may serve as an ideal antimicrobial agent., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Oligopeptides, a type of short peptide, which consist of 2-20 amino acids, exhibit a variety of biological functions in drug delivery systems, such as specific targeting, cell penetration, self-assembled capacity and responsiveness to the environment. In this review, we aim to highlight the importance of functional oligopeptides for nanomedical applications and put forward the views on the future development direction of oligopeptide medicines. Oligopeptides have gained wide attentions due to their inherent properties, but the lack of understanding the mechanisms of in vivo transport behavior is the biggest problem and challenge at the present stage. Therefore, it is an important direction for the future clinical research to systematically evaluate its metabolic behavior and safety in vivo.