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ObjectivesTo observe the efficacy of botulinum toxin type A (BoNT-A) for the spasticity of the lower-limb post-stroke on gait and posture control.MethodsA total of 46 patients with hemiplegia gait were randomly divided into the experimental group (23 patients) and the control group (23 patients). In patients in the experimental group received injections of BoNT-A by electrical stimulation-guided. At the same time, patients of the two groups received routine physical therapy. Gait analysis, plantar pressure analysis, lower-limb Fugl–Meyer assessment (L-FMA), 10 meter walking test (10MWT), timed “Up and Go” test (TUGT), and modified Ashworth Scale assess (MAS) of the lower limbs were performed at 0, 1, 4, and 12 weeks after treatment.ResultsAt 1, 4, and 12 weeks after treatment, the L-FMA, stride length, speed, and TUGT significantly improved than 0 week in both groups. The L-FMA and peak of forefoot pressure, and MAS results in the experimental group were better than those in the control group at 4 and 12 weeks. The TUGT, speed, and stride length in experimental group was significantly shortened than that in control group at 1, 4, and 12 weeks.ConclusionBotulinum toxin type A injection can improve motor functions of the lower limb, gait, spasticity, forefoot pressure, and posture control of patients after stroke.

Cytochrome P450 system consists of P450 monooxygenase and redox pattern(s). While the importance of monooxygenases in plant metabolism is well documented, the metabolic roles of the related redox components have been largely overlooked. Here, we show that distinct electron transfer chains are recruited in phenylpropanoid-monolignol P450 systems to support the synthesis and distribution of different classes of phenolics in different plant tissues. While Arabidopsis cinnamate 4-hydroxylase adopts conventional NADPH-cytochrome P450 oxidoreductase (CPR) electron transfer chain for its para -hydroxylation reaction, ferulate 5-hydroxylase uses both NADPH-CPR-cytochrome b 5 (CB5) and NADH–cytochrome b 5 reductase–CB5 chains to support benzene ring 5-hydroxylation, in which the former route is primarily recruited in the stem for syringyl lignin synthesis, while the latter dominates in the syntheses of 5-hydroxylated phenolics in seeds and seed coat suberin. Our study unveils an additional layer of complexity and versatility of P450 system that the plants evolved for diversifying phenolic repertoires.

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear.ObjectiveTo explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI).Study design and methodsThe hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearman’s correlation.ResultsChlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)/RAC-beta serine/threonine-protein kinase (AKT2)/forkhead box protein O1 (FOXO1)/glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2.ConclusionSMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1/AKT2/FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM).

Ectopic fat deposition in the liver, known as non-alcoholic fatty liver disease (NAFLD), affects up to 30% of the worldwide population. miRNA-122, the most abundant liver-specific miRNA, protects hepatic steatosis and inhibits cholesterol and fatty acid synthesis in NAFLD. Previously, we have shown that compared with its expression in healthy controls, miRNA-122 decreased in the liver tissue but gradually increased in the serum of patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, suggesting that miRNA-122 could have been transported to the serum. Here, we aimed to confirm and unravel the mechanism of transportation of miRNA-122 to extra-hepatocytes. Our findings showed a decrease in the intra-hepatocyte miRNA-122 and an increase in the extra-hepatocyte (medium level) miRNA-122, suggesting the miRNA-122 “escaped” from the intra-hepatocyte due to an increased extra-hepatocyte excretion. Using bioinformatics tools, we showed that miRNA-122 binds to circPI4KB, which was further validated by an RNA pull-down and luciferase reporter assay. The levels of circPI4KB in intra- and extra-hepatocytes corresponded to that of miRNA-122, and the overexpression of circPI4KB increased the miRNA-122 in extra-hepatocytes, consequently accomplishing a decreased protective role of miRNA-122 in inhibiting the lipid deposition. The present study provides a new explanation for the pathogenesis of the hepatic lipid deposition in NAFLD.

Background The Ferula genus encompasses 180–185 species and is one of the largest genera in Apiaceae, with many of Ferula species possessing important medical value. The previous studies provided more information for Ferula, but its infrageneric relationships are still confusing. In addition, its genetic basis of its adaptive evolution remains poorly understood. Plastid genomes with more variable sites have the potential to reconstruct robust phylogeny in plants and investigate the adaptive evolution of plants. Although chloroplast genomes have been reported within the Ferula genus, few studies have been conducted using chloroplast genomes, especially for endemic species in China. Results Comprehensively comparative analyses of 22 newly sequenced and assembled plastomes indicated that these plastomes had highly conserved genome structure, gene number, codon usage, and repeats type and distribution, but varied in plastomes size, GC content, and the SC/IR boundaries. Thirteen mutation hotspot regions were detected and they would serve as the promising DNA barcodes candidates for species identification in Ferula and related genera. Phylogenomic analyses with high supports and resolutions showed that Talassia transiliensis and Soranthus meyeri were nested in the Ferula genus, and thus they should be transferred into the Ferula genus. Our phylogenies also indicated the monophyly of subgenera Sinoferula and subgenera Narthex in Ferula genus. Twelve genes with significant posterior probabilities for codon sites were identified in the positively selective analysis, and their function may relate to the photosystem II, ATP subunit, and NADH dehydrogenase. Most of them might play an important role to help Ferula species adapt to high-temperatures, strong-light, and drought habitats. Conclusion Plastome data is powerful and efficient to improve the support and resolution of the complicated Ferula phylogeny. Twelve genes with significant posterior probabilities for codon sites were helpful for Ferula to adapt to the harsh environment. Overall, our study supplies a new perspective for comprehending the phylogeny and evolution of Ferula.

In this study, we investigated the role of tumor microenvironment and serum differential metabolites in intrahepatic cholangiocarcinoma (ICC) carcinogenesis, providing new evidence for ICC treatment. Serum samples from healthy individuals and ICC patients were collected for metabolomic analysis. The purine metabolites such as inosine, guanosine, hypoxanthine, and xanthine were increased in patient serum. TCGA database samples were collected, and the correlation between purine metabolism-related genes and ICC clinical features was analyzed using R language to obtain the differential genes including PPAT, PFAS, ATIC, and IMPDH2. High PPAT expression was associated with poor ICC prognosis. A PPAT silencing model in HCCC-9810 cells was constructed. The cell phenotype was examined by qRT-PCR, CCK-8, transwell, and flow cytometry, showing a decrease in IMPDH1 expression, colony and invasive cells numbers, and an increase in apoptosis. Guanosine reversed IMPDH1 expression in HCCC-9810 cells, promoting the secretion of inflammatory factors IL-6, IL-8, OPN, VEGF, and VCAM-1 and intensifying epithelial-mesenchymal transition (EMT) progression in the cells. In nude mice, the IMPDH1 inhibitory drug MMF inhibited tumor growth and reduced the expression of tumor stem cell characteristic markers CD133 and SOX2. Guanosine accelerated the malignant progression of ICC inhibition of purine metabolism-related genes, PPAT and IMPDH2, suppressed the malignant phenotype in HCCC-9810 cells, and inhibited tumor growth.

Detailed contact angle measurements are performed for protein drops on phenylcarbamide (PC), polymethyl methacrylate (PMMA), silicon nitride, and glass substrates by goniometer-sessile drop technique. Drop sizes are ranged from 0.1 to 6 w l with radius of curvature less than 1 mm. The bovine serum albumin (BSA) protein concentrations are 0.0, 0.1, 1.0, and 10 mg/ml. The results show weak dependence of the drop size for deionized water drops on all substrates and increased dependence of the drop size for protein drops with different protein concentrations. The significance of drop size effect varies from substrate to substrate; the effect is strongest for PC substrate, which is a nearly hydrophobic surface. The drop size dependence can be partly explained by the modified Young's equation.

Kitagawia Pimenov is one of the segregate genera of Peucedanum sensu lato within the Apiaceae. The phylogenetic position and morphological delimitation of Kitagawia have been controversial. In this study, we used plastid genome (plastome) and nuclear ribosomal DNA (nrDNA) sequences to reconstruct the phylogeny of Kitagawia, along with comparative plastome and morphological analyses between Kitagawia and related taxa. The phylogenetic results identified that all examined Kitagawia species were divided into Subclade I and Subclade II within the tribe Selineae, and they were all distant from the representative members of Peucedanum sensu stricto. The plastomes of Kitagawia and related taxa showed visible differences in the LSC/IRa junction (JLA) and several hypervariable regions, which separated Subclade I and Subclade II from other taxa. Fruit anatomical and micromorphological characteristics, as well as general morphological characteristics, distinguished the four Kitagawia species within Subclade I from Subclade II and other related genera. This study supported the separation of Kitagawia from Peucedanum sensu lato, confirmed that Kitagawia belongs to Selineae, and two species (K. praeruptora and K. formosana) within Subclade II should be placed in a new genus. We believe that the “core” Kitagawia should be limited to Subclade I, and this genus can be distinguished by the association of a series of morphological characteristics. Overall, our study provides new insights into the phylogeny, plastome evolution, and taxonomy of Kitagawia.

A novel near-infrared (NIR) fluorescent probe (SWJT-9) was designed and synthesized for the detection of hypochlorite anion (ClO−) using a diaminomaleonitrile group as the recognition site. SWJT-9 had large Stokes shift (237 nm) and showed an excellent NIR fluorescence response to ClO− with the color change under the visible light. It showed a low detection limit (24.7 nM), high selectivity, and rapid detection (within 2 min) for ClO−. The new detection mechanism of SWJT-9 on ClO− was confirmed by 1H NMR, MS spectrum, and the density functional theory (DFT) calculations. In addition, the probe was successfully used to detect ClO− in HeLa cells.

Insect chitinases play a crucial part to digest chitin in the exoskeleton during the molting process. However, research on insect chitinase related to the environmental stress response is very limited. This study was the first conducted to expression analysis of chitinase- related genes in A. pisum under abiotic stresses. Here, we identified five chitinase-like proteins (ApIDGF, ApCht3, ApCht7, ApCht10 and ApENGase), and clustered them into five groups (group II, III, V, Ⅹ, and ENGase). Developmental expression analysis revealed that the five A. pisum chitinase-related genes were expressed at whole developmental stages with different relative expression patterns. When aphids were exposed to various abiotic stresses including temperature, insecticide and the stress 20-hydroxyecdysone (20E), all five chitinase genes were differentially expressed in A. pisum. The results showed that insecticide such as imidacloprid down-regulated the expression of these five Cht-related genes. Analysis of temperature stress of A. pisum chitinase suggested that ApCht7 expression was high at 10°C, which demonstrates its important role in pea aphids under low temperature. Conversely, ApCht10 was more active under high temperature stress, as it was significantly up-regulated at 30°C. Besides, 20E enhanced ApCht3 and ApCht10 expression in A. pisum, but reduced ApCht7 expression. These findings provide basic information and insights for the study of the role of these genes under abiotic stress, which advances our knowledge in the management of pea aphids under multiple stresses.

Mutations in AT-rich interactive domain-containing protein 1A (ARID1A) cause Coffin-Siris syndrome (CSS), a rare genetic disorder that results in mild to severe intellectual disabilities. However, the biological role of ARID1A in the brain remains unclear. In this study, we report that the haploinsufficiency of ARID1A in excitatory neurons causes cognitive impairment and defects in hippocampal synaptic transmission and dendritic morphology in mice. Similarly, human embryonic stem cell-derived excitatory neurons with deleted ARID1A exhibit fewer dendritic branches and spines, and abnormal electrophysiological activity. Importantly, supplementation of acetate, an epigenetic metabolite, can ameliorate the morphological and electrophysiological deficits observed in mice with Arid1a haploinsufficiency, as well as in ARID1A-null human excitatory neurons. Mechanistically, transcriptomic and ChIP-seq analyses demonstrate that acetate supplementation can increase the levels of H3K27 acetylation at the promoters of key regulatory genes associated with neural development and synaptic transmission. Collectively, these findings support the essential roles of ARID1A in the excitatory neurons and cognition and suggest that acetate supplementation could be a potential therapeutic intervention for CSS.

Background The genus Seseli L., which consists of 125–140 species distributed in the Old World from western Europe and northwestern Africa to China and Japan, is one of the largest and most taxonomically difficult genera of Apiaceae Lindl. Although several previous studies have been conducted on Seseli based on limited morphological characteristics and molecular fragments, a robust and comprehensive phylogeny of Seseli remains elusive. Plastomes provide abundant genetic information and have been widely used in studying plant phylogeny and evolution. Consequently, we newly generated the complete plastomes of eleven Seseli taxa. We combined plastome data and morphological characteristics to investigate the phylogeny of Seseli. Results In our study, we observed that the genome length, gene numbers, IR/SC borders, and repeat composition of the eleven Seseli plastomes were variable. Several appropriate mutation hotspot regions may be developed as candidate DNA barcodes for evolution, phylogeny, and species identification of Seseli. The phylogenetic results identified that Seseli was not a monophyletic group. Moreover, the eleven newly sequenced Seseli taxa did not cluster with S. tortuosum (the type species of Seseli, belonging to the tribe Selineae), where S. delavayi clustered with Eriocycla belonging to the tribe Echinophoreae and the other ten belonged to Selineae. The comparative plastome and morphological characteristics analyses confirmed the reliability of the phylogenetic analyses and implied the complex evolution of Seseli. Conclusion Combining molecular and morphological data is efficient and useful for studying the phylogeny of Seseli. We suggest that “a narrow sense” of Seseli will be meaningful for further study and the current taxonomic system of Seseli needs to be revised. In summary, our study can provide new insights into the phylogenetic relationships and taxonomic framework of Seseli.

Abdominal aortic aneurysm(AAA) is a chronic dilated artery disease induced by atherosclerosis,infection,trauma and other related causes.The available studies about AAA mainly focus on the inflammatory response,senility,and microenvironmental changes,while the research on the metabolic changes such as glucose metabolism and lipid metabolism remains to be conducted.As a critical regulatory factor in endocrine,glucose,and lipid metabolisms,leptin is associated with a variety of signaling pathways such as adenosine monophosphate-activated protein kinase,Janus kinase/signal transducer and activator of transcription,and cytokine-cytokine receptor,as demonstrated by the KEGG pathway enrichment analysis.Moreover,these signaling pathways are generally involved in regulating the occurrence of AAA.In addition,leptin affects the occurrence of a variety of diseases such as obesity,diabetes,and hyperlipidemia,which contribute to the formation of AAA.Diabetes might be a protective factor for the formation of AAA,while the relationship of hyperlipidemia and obesity with the formation of AAA remains unclear.Therefore,leptin might play an essential role in the formation of AAA.Further studies about the effect of leptin on AAA may provide the potential research direction and facilitate the discovery of therapeutic targets.

Fucosylation is one of the most common modifications of oligo-N-acetyllactosamine (oligo-LacNAc) glycans. However, none of known fucosyltransferases (FucTs) could install the α1,3-linked fucose to the oligo-LacNAc substrates in a site-specific manner. Here, we report a facile and general redox-controlled substrate engineering strategy for the site-specific α1,3-fucosylation of complex glycans containing multiple LacNAc units. This strategy takes advantage of an operationally simple oxidation enzyme module by using galactose oxidase (GOase) to convert the LacNAc unit into oxidized C6'-aldehyde LacNAc sequence, which is not a good substrate for recombinant α1,3-FucT from Helicobacter pylori strain 26695 (Hpα1,3FucT), enabling the site-specific α1,3-fucosylation at intact LacNAc sites. The general applicability and robustness of this strategy were demonstrated by the synthesis of a variety of structurally well-defined fucosides of linear and branched O- and N-linked glycans.

A Frisch-grid Ionization Chamber (FGIC) for the measurement of low activity of alpha-particle emitters has been built. The design and performance are described in this paper. According to the Shockley–Ramo theorem and the experiment, the key parameter grid inefficiency was studied in detail. The experimental and calculated values of the correction factor are shown to be in good agreement. In the measurement of the alpha-activities of a 234,238U sample, the detection efficiency was investigated based on the Monte-Carlo method. Considering this influence, the activity of alpha-particle emitters was identified.

Background/purpose Growth arrest-specific 6 (Gas6) protein is involved in cell proliferation, differentiation, adhesion, migration in response to inflammatory processes. Human immunodeficiency virus (HIV) infection induces a chronic inflammatory condition and combination of antiretroviral therapy improves immune function and decreases the inflammatory state. The aim of this study was to assess the implications of Gas6 in chronic inflammation status of HIV-infected patients undergoing different third regimens of antiretroviral therapy. The Gas6 may be a marker of chronic inflammation of HIV-infected patients. Methods A total of 356 adult males, including 258 HIV-infected patients and 98 healthy controls, were recruited. The demographic and clinical characteristics of the patients were collected. Laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), hepatitis B and C viruses, and serum biochemistry. Plasma Gas6 concentrations were determined. Results The values of Gas6 were lower in HIV patients compared to healthy subjects (14.3 ± 6.4 vs 21.5 ± 15.2, p = 0.01). HIV patients that received antiviral regimen with abacavir had similar Gas6 level than those who received antiviral regimens with tenofovir (14.3 ± 6.5 vs 13.8 ± 5.9, p = 0.99). HIV patients that received antiviral regimen with protease inhibitors (PIs) had lower Gas6 level (13.1 ± 3.5 vs 14.2 ± 6.6 vs 14.6 ± 6.5, p = 0.03) than those who received antiviral regimens with non-nucleoside reverse transcriptase inhibitors (nNRTIs) and integrase inhibitors (INSTIs), respectively. Conclusions Decreased plasma Gas6 concentrations were observed in HIV patients. Gas6 levels are associated with different third regimen of highly active antiretroviral therapy. Gas6 may represent a unique marker for assessing the chronic inflammation state difference among cART regimens in HIV patients.

Traditional approaches to the directed evolution of genes of interest (GOIs) place constraints on the scale of experimentation and depth of evolutionary search reasonably achieved. Engineered genetic systems that dramatically elevate the mutation of target GOIs in vivo relieve these constraints by enabling continuous evolution, affording new strategies in the exploration of sequence space and fitness landscapes for GOIs. We describe various in vivo hypermutation systems for continuous evolution, discuss how different architectures for in vivo hypermutation facilitate evolutionary search scale and depth in their application to problems in protein evolution and engineering, and outline future opportunities for the field.

Sensible but Cool Advances in Protein Chemistry Investigators have exploited redundancy in the genetic code to engineer proteins with unnatural amino acids. They have similarly rendered “synonymize...

Biomedical patches play fundamental roles in various applications such as wound closure and tissue regeneration. The hybrid patches integrating versatile properties will prominently improve the therapeutic effects in clinical applications. Herein, an epoxy network loading curcumin and Ti3C2Tx MXenes were developed as a hybrid biomedical patch. The hybrid patch was basically prepared through an epoxy/thiol curing chemistry, and its topological structure can be destructed and rearranged as a vitrimer does due to the active transesterification at high temperature. The resulted hybrid patch exhibits shape-morphing capability, multi-substrate adhesion, self-healing ability, and photothermal effects under 980 nm near infrared (NIR). Additionally, the as-prepared hybrid patch possesses strong UV-shielding, excellent oxidation resistance (ROS scavenging efficiency was 89.3% in 3 min), highly effective antibacterial vitality (more than 99%) against S. aureus and E. coli, and good cytocompatibility. As a proof of concept, the present multifunctional hybrid patch broadens the potential applications in the biomedical field.

Background and Objectives: Our study aimed to explore the therapeutic effects of surgical clipping and endovascular embolization on the recovery of oculomotor nerve paralysis (ONP) caused by posterior communicating artery aneurysm (PcomAA). Methods: The clinical data of patients with intracranial PcomAA and ONP were retrospectively analyzed. All patients were treated with surgical clipping or endovascular embolization, then followed up for no less than 12 months. Logistic regression analysis was performed to analyze the potential risk factors influencing ONP recovery. Results: Among 128 patients of ONP caused by PcomAA, 96 patients were treated with surgical clipping and 32 patients with endovascular embolization, respectively. Time from initial ONP onset to complete or partial recovery was 85.3 ± 36.8 days for patients receiving surgical clipping, and 135.7 ± 41.3 days for patients treated with endovascular embolization. The recovery rate was 94 (97.9%) in the surgical clipping group and 22 (68.8%) in the endovascular embolization group, and significant difference was shown between the two groups (P < 0.001). Logistic regression analyses demonstrated that the complete or partial recovery of ONP in the surgical clipping group was significantly better than that in the endovascular embolization group (OR, 5.582; 95%CI, 2.023-15.405; P

We aimed to explore the effects of Fallopia multiflora–Andrographis paniculata intercropping model on yield, quality, soil nutrition and rhizosphere microorganisms of F. multiflora, an important raw material of a traditional Chinese medicine. The data will provide empirical evidence for the application and promotion of the system in agricultural production. F. multiflora’s yield, potential medicinal quality, and rhizosphere soil nutrient contents, pH, enzyme activities, and microbial characteristics (such as diversity and structure of the bacterial community) were compared between the intercropped system and a monoculture of F. multiflora. Compared with the monoculture of F. multiflora, F. multiflora–A. paniculata intercropping significantly increased the stem diameter, root fresh weight, yield and stilbene glycoside content of F. multiflora. The activities of urease and sucrase and the amounts of bacteria and actinomycetes in rhizosphere soil of intercropped F. multiflora were significantly higher than those in rhizosphere soil of the monoculture. Intercropping increased the diversity of rhizosphere bacteria and the relative abundances of potentially beneficial microorganisms. Correlation analysis shows that the yield and quality of F. multiflora were closely related to urease and invertase activities, alkaline hydrolysis nitrogen content, soil organic matter content, bacterial biomass, and pH. The results of principal component analysis show that the score of intercropping soil was higher than that of monoculture soil. A. paniculata intercropping has a significant impact on the rhizosphere soil of F. multiflora, and can improve the yield and quality of F. multiflora by improving the rhizosphere soil ecological environment and soil quality.

We report herein a novel delivery system, derived from the facile enzymatic synthesis of oligorutin (OR), for cancer cell targeting and pH-responsive drug delivery. In this study, we demonstrate that OR could preferentially penetrate cancer cells via the lipid raft-mediated endocytosis pathway, and cell membrane cholesterol was critical to the internalization of OR. The accumulation of OR in the tumor region was further confirmed by an in vivo biodistribution study. Considering the tumor-targeting property of OR, a pH-responsive drug delivery system (OR-BTZ) was developed by covalent conjugation of the catechol groups on OR with antitumor drug bortezomib (BTZ) through a pH-sensitive borate ester bond. OR-BTZ exerted cytotoxicity as well as inhibition of the migration and invasion to hepatoma carcinoma cells and showed no apparent cytotoxicity with liver normal cells. The OR-BTZs also presented significant therapeutic efficacy and low systematic toxicity in the murine hepatocellular carcinoma model. To our knowledge, this study presents the first attempt to exploit the potential of oligoflavonoids for cancer cell-targeted drug delivery and will motivate the development of flavonoids and their derivatives as a new type of biomaterials for tumor-targeted therapy.

Plant lignification exhibits notable plasticity. Lignin in many species, including Populus spp., has long been known to be decorated with p-hydroxybenzoates. However, the molecular basis for such structural modification remains undetermined. Here, we report the identification and characterization of a Populus BAHD family acyltransferase that catalyses monolignol p-hydroxybenzoylation, thus controlling the formation of p-hydroxybenzoylated lignin structures. We reveal that Populus acyltransferase PHBMT1 kinetically preferentially uses p-hydroxybenzoyl-CoA to acylate syringyl lignin monomer sinapyl alcohol in vitro. Consistently, disrupting PHBMT1 in Populus via CRISPR–Cas9 gene editing nearly completely depletes p-hydroxybenzoates of stem lignin; conversely, overexpression of PHBMT1 enhances stem lignin p-hydroxybenzoylation, suggesting PHBMT1 functions as a prime monolignol p-hydroxybenzoyltransferase in planta. Altering lignin p-hydroxybenzoylation substantially changes the lignin solvent dissolution rate, indicative of its structural significance on lignin physiochemical properties. Identification of monolignol p-hydroxybenzoyltransferase offers a valuable tool for tailoring lignin structure and physiochemical properties and for engineering the industrially important platform chemical in woody biomass. p-Hydroxybenzoylation is a common type of lignin modification but its catalytic mechanism and physiological relevance are unclear. An enzyme that catalyses lignin p-hydroxybenzoylation in poplar sheds light on the role of this specialized modification.

Background CBA/J mice are standard experimental animals in auditory studies, and age-related changes in auditory pathways are well documented. However, changes in locomotion-related brain regions have not been systematically explored. Results We showed an increase in immunoreactivity for glial fibrillary acidic protein (GFAP) in the cerebellar molecular layer associated with Purkinje cells in mice at 24 weeks of age but not in the younger mice. Increased GFAP immunoreactivity appeared in the form of clusters and distributed multifocally consistent with hyperplasia of astrocytes that were occasionally associated with Purkinje cell degeneration. Three out of 12 animals at 16 and 24 weeks of age exhibited pre-convulsive clinical signs. Two of these 3 animals also showed increased GFAP immunoreactivity in the cerebellum. Rotarod behavioral assessments indicated decreased performance at 24 weeks of age. Conclusions These results suggest minimal to mild reactive astrocytosis likely associated with Purkinje cell degeneration in the cerebellum at 24 weeks of age in CBA/J mice. These findings should be taken into consideration prior to using this mouse strain for studying neuroinflammation or aging.