Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review.

Diabetic kidney disease (DKD) is a long-term and serious complication of diabetes that affects millions of people worldwide. It is characterized by proteinuria, glomerular damage, and renal fibrosis, leading to end-stage renal disease, and the pathogenesis is complex and involves multiple cellular and molecular mechanisms. Among three kinds of intraglomerular cells including podocytes, glomerular endothelial cells (GECs) and mesangial cells (MCs), the alterations in one cell type can produce changes in the others. The cell-to-cell crosstalk plays a crucial role in maintaining the glomerular filtration barrier (GFB) and homeostasis. In this review, we summarized the recent advances in understanding the pathological changes and interactions of these three types of cells in DKD and then focused on the signaling pathways and factors that mediate the crosstalk, such as angiopoietins, vascular endothelial growth factors, transforming growth factor-ß, Krüppel-like factors, retinoic acid receptor response protein 1 and exosomes, etc. Furthermore, we also simply introduce the application of the latest technologies in studying cell interactions within glomerular cells and new promising mediators for cell crosstalk in DKD. In conclusion, this review provides a comprehensive and updated overview of the glomerular crosstalk in DKD and highlights its importance for the development of novel intervention approaches.

Genetic basis investigation of wattle phenotype in goat using genome-wide sequence data.

In domestic goats, wattles often appear in even numbers, mostly on the neck and a few under the ear. Goat wattle is composed of ectopic cartilage tissue covered by skin and was reported as a dominant inheritance. Thirty-eight goats from two Southwest Chinese breeds were studied to elucidate the genetic basis of wattle phenotype in goat. Their genomes were sequenced for wide-genome selective sweep analysis (WGSA) and a genome-wide association study (GWAS). The WGSA results revealed 500 candidate genes identified by fixation index and π ratio and 261 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched with 195 genes and 38 significantly enriched KEGG items. In particular, three chondrogenesis-related pathways (Wnt, Hippo and MAPK signaling pathways) were found. Among the 500 genes, 474 were enriched to 2855 Gene Ontology items, and four (BMP2, BMP4, RARA and MSX1) were annotated in the regulation and development of chondrogenesis. Four chondrogenesis-related genes (GREM1, NEDD4, ATG7 and ITGA1) were identified from 519 single-nucleotide polymorphisms (SNPs) with a GWAS above the threshold. Six and 11 SNPs on chromosome 10 are located on GREM1 and NEDD4 respectively, and the highest numbers of SNPs on chromosomes 20 and 22 are located on ITGA1 and ATG7 respectively. All of these genes are related to cartilage development. This study identified a series of genes related to chondroplasia by GWAS and WGSA and presented the possibility that wattle inheritance may be influenced by multiple genes. This work provides a new theoretical understanding of the hereditary basis of wattle phenotype.

Influencing factors of end-of-dose failure in patients with cancer pain after oral oxycodone sustained-release tablets: a retrospective, case-control study.

OBJECTIVE: Comparing the characteristics of end-of-dose failure patients and non-end-of-dose failure patients in the Chinese population and exploring the factors that may affect the occurrence of end-of-dose failure in cancer pain patients. METHODS: The outpatient with cancer pain from 2016 to 2019 were collected through hospital information system, and patients were included who met the following criteria: patients with the average numerical rating scale  ≥4 points within 3 days after taking the oxycodone sustained-release preparation, titrated to an effective therapeutic dose suitable for patients, had at least two clinical visits information of the patient with a minimum of ≥3 days between visits, the average numerical rating scale of the next visit after the treatment of occasional pain is ≥4, and were divided into end-of-dose failure group and non-end-of-dose failure group. RESULTS: Age (P < 0.05, odds ratio 0.933), diagnosis of nasopharyngeal carcinoma (P < 0.05, odds ratio 0.009), pain site is the head and neck (P < 0.05, odds ratio 0.005) and the abdomen (P < 0.01, odds ratio 0.021), and the metastatic site is the liver (P < 0.05, odds ratio 0.001) are related to the occurrence of end-of-dose failure. CONCLUSIONS: Younger patients are more likely to develop end-of-dose failure. Patients diagnosed with nasopharyngeal cancer, with pain in the head and neck and abdomen, and with liver metastases have a lower incidence of end-of-dose failure.

Effect of CYP2C9 genetic polymorphism and breviscapine on losartan pharmacokinetics in healthy subjects.

1. Breviscapine was an active ingredient of flavonoid glycosides. Our present study was conducted to evaluate the impact of breviscapine on the pharmacokinetics of losartan and its active metabolite E-3174, and that relationship with the gene polymorphism of CYP2C9 in healthy Chinese volunteers, to provide a basis for clinical rational drug use.2. The genotypes of 217 healthy Chinese subjects were determined using PCR-RFLP. Twelve healthy subjects were selected and were known CYP2C9 genotypes (six CYP2C9*1/*3 and six CYP2C9*1/*1) in a two-phase randomised crossover design study. These subjects were given daily doses of 120 mg (40 mg, three times a day) of breviscapine or a placebo for 14 days, followed by 50 mg losartan on day 15.3. Compared with individuals carrying the CYP2C9*1/*1 genotype, the CYP2C9*1/*3 genotype showed an increase in the AUC(0-36) (833.6 ± 379.8 ng h ml-1 vs. 526.1 ± 140.1 ng h ml-1, p < 0.05) and a decrease in the MR (the metabolic ratio of losartan, AUCE-3174/AUClosartan) (2.67 ± 1.40 vs. 4.56 ± 0.83, p < 0.05) of losartan during the placebo treatment phase. Individuals with genotype CYP2C9*1/*3 showed a significant increase in AUC(0-36) (2335 ± 851.8 ng h ml-1 vs. 1927 ± 949.5 ng h ml-1, p < 0.05) and AUC(0-∞) (2363 ± 875.6 ng h ml-1 vs. 1966 ± 966.1 ng h ml-1, p < 0.05) of E-3174 after breviscapine treatment compared to the placebo group.4. In healthy subjects, breviscapine had no significant effect on the pharmacokinetics of losartan. The activity of CYP2C9 enzyme to losartan metabolism was more significant in subjects with CYP2C9*1/*3 than those with CYP2C9*1/*1 genotype.

Emticicia soli sp. nov., a novel member of the family 'Flexibacteraceae', isolated from tetrabromobisphenol A-contaminated soil.

Bacterial strain ZZ-4T, a Gram-stain-negative, aerobic, non-spore-forming, non-motile, non-flagellated, rod-shaped bacterium, was isolated from tetrabromobisphenol A-contaminated soil in PR China. The taxonomic position of this strain was investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ZZ-4T was a member of the genus Emticicia and showed the highest sequence similarity to Emticicia fontis IMCC1731T (98.0 %) and Emticicia ginsengisoli Gsoil 085T (97.2 %), and lower (<97 %) sequence similarity to other known Emticicia species. Chemotaxonomic analysis revealed that strain ZZ-4T possessed menaquinone MK-7 as the major isoprenoid quinone; and iso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7), iso-C17 : 0 3-OH and C16 : 1ω5c were the predominant fatty acids. Strain ZZ-4T showed low DNA-DNA relatedness with E. fontis IMCC1731T (39.8±3.1 %) and E. ginsengisoli Gsoil 085T (44.51±1.5 %). The DNA G+C content was 38.3 mol%. Based on the phylogenetic and phenotypic characteristics, chemotaxonomic data and DNA-DNA hybridization results, strain ZZ-4T is considered to represent a novel species of the genus Emticicia, for which the name Emticicia soli sp. nov. is proposed. The type strain is ZZ-4T (=KCTC 52344T=CCTCC AB 2016137T).

Terrimonas suqianensis sp. nov., isolated from a tetrabromobisphenol A-contaminated soil.

Strain C3-5T, a Gram-negative, asporogenous, rod-shaped bacterium, was isolated from a tetrabromobisphenol A contaminated soil. Growth was observed at 10-37 °C (optimum 30 °C) and at pH 5.5-9.5 (optimum pH 7.0). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain C3-5T is a member of the genus Terrimonas and exhibits high sequence similarities with Terrimonas pekingensis QHT (99.0%) and Terrimonas rhizosphaerae CR94T (97.3%), and exhibits low (<97%) sequence similarities with other known Terrimonas species. Chemotaxonomic analysis revealed that strain C3-5T possesses menaquinone-7 (MK-7) as the major isoprenoid quinone and iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH and summed feature 3 (C16:1 ω6c and/or C16:1 ω7c) as the major (>5% of total) fatty acids. The polar lipids were determined to be a lipid, glycolipid, phospholipid, phosphoaminolipid and phosphatidylethanolamine. The DNA G+C content was found to be 42.6 mol%. The DNA-DNA relatedness values with the closely related strains T. pekingensis QHT and T. rhizosphaerae CR94T were 25.2 and 48.5%, respectively. Based on phylogenetic analysis, phenotypic characteristics and chemotaxonomic data, strain C3-5T is considered to represent a novel species of the genus Terrimonas, for which the name Terrimonas suqianensis sp. nov. is proposed. The type strain is C3-5T (= CCTCC AB 2017042T = KCTC 52676T).

Facile Preparation of Bright-Fluorescent Soft Materials from Small Organic Molecules.

Highly fluorescent and biocompatible soft materials are desirable for many potential applications, but their synthetic processes are somehow complicated. Herein, we have explored the feasibility of synthesis of unconventional fluorescence soft materials from small organic molecules under mild conditions. A new blue-fluorescent soft material with high quantum yield (89.6 %) and eutectic feature prepared by simple heat treatment of citric acid (CA) and cysteine (Cys) aqueous mixtures below 100 °C in air was reported. The as-prepared fluorescent material has the features of facile preparation, low cost, scalable production and easy to process, making it suitable for applications like fluorescent labeling and light-emitting devices. This new finding opens a new venue for the preparation of fluorescent soft materials.

Graphene oxide/carbon dot composite: a new photoelectrode material for photocurrent response enhancement.

Low-dimensional carbon nanocomposite-based architectures and anchoring zero-dimensional carbon dots on two-dimensional graphene sheets may provide an important approach to develop energy harvesting and conversion strategies. In this work, as a novel photoelectrode with a high photocurrent response performance based on a composite made with all carbon-based materials consisting of p-type graphene oxide (GO) and n-type nitrogen, sulfur co-doped carbon dot (NS-CD) has been prepared via the electrophoretic deposition approach. The photoelectrochemical measurement shows that the GO/NS-CD composite greatly suppresses the charge recombination and evidently enhances the photocurrent response activity. It is anticipated that this work may pave a valuable step for the further development of all carbon-based optoelectronic devices with excellent performance.

Discovery of new pesticide candidates from nature: design, synthesis and bioactivity research of rutaecarpine derivatives.

BACKGROUND: The invasion of viruses and fungi can cause pathological changes in the normal growth of plants and is an important factor in causing plant infectious diseases. These pathogenic microorganisms can also secrete toxic metabolites, affecting crop quality and posing a threat to human health. In this work, we selected the natural product rutaecarpine as the lead compound to achieve the total synthesis and structural derivation. The antiphytoviral activities of these compounds were systematically studied using tobacco mosaic virus (TMV) as the tested strain, and the structure-activity relationships were summarized. RESULT: The anti TMV activities of compounds 5a, 5n, 6b, and 7c are significantly higher than that of commercial antiviral agent ningnanmycin. We chose 5n for further antiviral mechanism research, and the results showed that it can directly act on viral particles. The molecular docking results further confirmed the interaction of compound 5n and coat protein (CP). These compounds also exhibited broad-spectrum fungicidal activities against eight plant pathogens. Especially compounds 5j and 5p have significant anti-fungal activities (EC50: 5j, 1.76 µg mL-1; 5p, 1.59 µg mL-1) and can be further studied as leads for plant-based anti-fungal agents. CONCLUSION: The natural product rutaecarpine and its derivatives were synthesized, and evaluated for their anti-TMV and fungicidal activities. Compounds 5n and 5p with good activities emerged as new antiviral and anti-fungal candidates, respectively. This study provides important information for the research and development of the novel antiviral and fungicidal agents based on rutaecarpine derivatives. © 2024 Society of Chemical Industry.

Graphene in light: design, synthesis and applications of photo-active graphene and graphene-like materials.

Graphene functionalized with photo-active units has become one of the most exciting topics of research in the last few years, which remarkably sustains and expands the graphene boom. The rise of photo-active graphene in photonics and optoelectronics is evidenced by a spate of recent reports on topics ranging from photodetectors, photovoltaics, and optoelectronics to photocatalysis. For these applications, the fabrication of photo-active graphene through appropriate chemical functionalization strategies is essential as pristine graphene has zero bandgap and only weak absorption of photons. Written from the chemists' point of view, up-to-date chemical functionalization of graphene with various small organic molecules, conjugated polymers, rare-earth components, and inorganic semiconductors is reviewed. Particular attention is paid to the development of graphene functionalized with light-harvesting moieties, including materials synthesis, characterization, energy/charge-transfer processes, and applications in photovoltaics. Challenges currently faced by researchers and future perspectives in this field are also discussed.

Free-radical-promoted conversion of graphite oxide into chemically modified graphene.

The preparation of chemically modified graphene (CMG) generally involves the reduction of graphite oxide (GO) by using various reducing reagents. Herein, we report a free-radical-promoted synthesis of CMG, which does not require any conventional reductant. We demonstrated that the phenyl free radical can efficiently promote the conversion of GO into CMG under mild conditions and produces phenyl-functionalized CMG. This pseudo-"reduction" process is attributed to a free-radical-mediated elimination of the surface-attached oxygen-containing functionalities. This work illustrates a new strategy for preparing CMG that is alternative to the conventional means of chemical reduction. Furthermore, the phenyl-functionalized graphene shows an excellent performance as an electrode material for lithium-battery applications.

Sequencing of the first ayu (Plecoglossus altivelis) macrophage transcriptome and microarray development for investigation the effect of LECT2 on macrophages.

Macrophages play an important role in first-line host defense of innate immune in fishes. However, it is difficult to investigate cellular mechanism of immune response in fish species with little genomic information available. Here we present the first use of RNA-Sequencing to study the macrophage transcriptome of ayu, Plecoglossus altivelis, which is an economically important fish in East Asia. De novo assembly generated 49,808 non-redundant consensus sequences, among which 23,490 transcripts found respective coding sequences. 15,707 transcripts are predicted to be involved in known metabolic or signaling pathways. The sequences were then used to develop a microarray for measurement the effect of recombinant LECT2 on ayu macrophages. LECT2 altered expression of a variety of genes mainly implicated in actin cytoskeleton, pattern recognition receptors and cytokines. Meanwhile, LECT2 enhanced phagocytosis, bacterial killing, and respiratory burst in ayu macrophages, which supported the thought derived from the microarray data that LECT2 activates macrophages. In conclusion, our results contribute to understanding the specific regulation mechanism of LECT2 in macrophage activation, and the combination of transcriptome analysis and microarray assay is a good method for screening a special tissue or cell response to a stimulus or pathogen in non-model fish species.

A Flexible Bivalent Approach to Comprehensively Improve the Performances of Stilbazolium Dyes as Amyloid-ß Fluorescent Probes.

Exploring new ways to reconstruct the structure and function of inappropriate organic fluorophores for improving amyloid-ß (Aß) fluorescent imaging performance is desired for precise detection and early diagnosis of Alzheimer's disease (AD). With stilbazolium dyes as examples, here, we present a multipronged approach to comprehensively improved the Aß fluorescent imaging performance through a flexible bivalent method, where a flexible carbon chain was introduced to link two monomers to form a homodimer. Our results reveal a mechanism wherein the flexible linker creates a well-defined probe with specific orientations and distinct photophysical properties. Applying this approach in combination with theoretical simulation, the homodimers exhibited a comprehensive improvement of the Aß fluorescent imaging performance of the dye monomers, including better photostability and higher signal-to-noise (S/N) ratio, higher "off-on" near-infrared fluorescence (NIRF) response sensitivity, higher specificity and affinity to Aß deposits, and more reasonable lipophilicity for blood-brain barrier (BBB) penetrability. The results demonstrate that flexible homodimers offer a multipronged approach to obtaining high-performance NIRF imaging reagents for the detection of Aß deposits both in vitro and in vivo.

Moshen granule ameliorates membranous nephropathy by blocking intrarenal renin-angiotensin system signalling via the Wnt1/ß-catenin pathway.

BACKGROUND: Membranous nephropathy (MN) is one of the cardinal causes of nephrotic syndrome in adults, but an adequate treatment regimen is lacking. PURPOSE: We assessed the effect of Moshen granule (MSG) on patients with MN and cationic bovine serum albumin (CBSA)-induced rats. We further identified the bioactive components of MSG and revealed the underlying molecular mechanism of its renoprotective effects. METHODS: We determined the effect of MSG on patients with MN and CBSA-induced rats and its components on podocyte injury in zymosan-activated serum (ZAS)-elicited podocytes and revealed their regulatory mechanism on the Wnt/ß-catenin/renin-angiotensin system (RAS) signalling axis. RESULTS: MSG treatment improved renal function and reduced proteinuria in MN patients and significantly reduced proteinuria and preserved the protein expression of podocin, nephrin, podocalyxin and synaptopodin in CBSA-induced MN rats. Mechanistically, MSG treatment significantly inhibited the protein expression of angiotensinogen, angiotensin converting enzyme and angiotensin II type 1 receptor, which was accompanied by inhibition of the protein expression of Wnt1 and ß-catenin and its downstream gene products, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in CBSA-induced MN rats. We further identified 81 compounds, including astragaloside IV (AGS), calycosin, barleriside A and geniposidic acid, that preserve the podocyte-specific protein expression in ZAS-induced podocytes. Among these four compounds, AGS exhibited the strongest inhibitory effects on podocyte protein expression. AGS treatment significantly inhibited the protein expression of RAS components and Wnt1 and ß-catenin and its downstream gene products in ZAS-induced podocytes. In contrast, the inhibitory effect of AGS on podocyte-specific proteins, ß-catenin downstream gene products and RAS components was partially abolished in ZAS-induced podocytes treated with ICG-001 and ß-catenin siRNA. CONCLUSION: This study first demonstrates that AGS mitigates podocyte injury by inhibiting the activation of RAS signalling via the Wnt1/ß-catenin pathway by both pharmacological and genetic methods. Therefore, AGS might be considered a new ß-catenin inhibitor that inhibits the Wnt1/ß-catenin pathway to retard MN in patients.

Monitoring the layer-by-layer self-assembly of graphene and graphene oxide by spectroscopic ellipsometry.

Thin films of graphene oxide, graphene and copper (II) phthalocyanine dye have been successfully fabricated by electrostatic layer-by-layer (LbL) assembly approach. We present the first variable angle spectroscopic ellipsometry (VASE) investigation on these graphene-dye hybrid thin films. The thickness evaluation suggested that our LbL assembly process produces highly uniform and reproducible thin films. We demonstrate that the refractive indices of the graphene-dye thin films undergo dramatic variation in the range close to the absorption of the dyes. This investigation provides new insight to the optical properties of graphene containing thin films and shall help to establish an appropriate optical model for graphene-based hybrid materials.

[Animal gene pyramiding in cross populations].

Gene pyramiding aims at producing individuals with one superior economic trait according to the optimal breeding scheme involving selection of favorable target alleles or linked markers after crossing basal populations and pyramiding them into a single individual. In consideration of animal traditional cross program along with the features of animal segregating population, four types of cross programs and two types of selection strategies for gene pyramiding are performed from practice perspective of view, two population cross for pyramiding two genes (denoted II), three populations cascading cross for pyramiding three genes (denoted III), four population symmetrical (denoted IV-S) and cascading cross for pyramiding four genes (denoted IV-C), and various schemes (denoted cross program-A-E) were designed for each cross program with different levels of initial favorable allele frequencies, basal population sizes, and trait heritabilities. The process of gene pyramiding for various schemes were simulated and compared based on the population hamming distance, average superior genotype frequencies, and average phenotypic values. By simulation, the results showed that larger base population size and higher initial favorite allele frequency resulted in higher efficiency of gene pyramiding. The order of parent crossing was shown to be the most important factor in cascading cross, but had no significant influence on the symmetric cross. The results also showed that genotypic selection strategy was superior to phenotypic selection in accelerating gene pyramiding. The method and corresponding software would be used to compare different cross schemes and selection strategies. Moreover, our study would help to build the optimal gene pyramiding simulation platform.

Near-infrared irradiation controlled thermo-switchable polymeric photosensitizer against ß-amyloid fibrillation.

Photothermal therapy (PTT) is an emerging paradigm for the degradation of amyloid-ß (Aß) aggregations and has become an effective way of treating Alzheimer's disease (AD). A promising PTT therapeutic option requires control of at least two key functional aspects: controllable photoactivity and specific activation. In this work, a near-infrared (NIR)-activated thermo-switchable biopolymeric PTT agent was designed and synthesized by conjugating a molecular rotor-based boron dipyrromethene photosensitizer (BDP) to a temperature-responsive polymer backbone of biopolymeric hydroxypropyl cellulose (HPC). The as-synthesized BDP-HPC exhibited an ultra-high PCE of 78.1% along with prominent cycling stability of phase-transition behavior under NIR irradiation in the light of the lower critical solution temperature (LCST at 42.5 °C). Importantly, the NIR irradiation can manipulate the reversible phase transition behavior of the resultant BDP-HPC that reveals high effectiveness in inhibiting Aß aggregation together with the obvious ability to dissociate Aß aggregations. Our work reveals an accurate modulation strategy for versatile and high-performance AD treatment.

Development of the Practice of Pharmaceutical Care for Cancer Pain Management in Outpatient Clinics Using the Delphi Method.

Background: There exists no broad agreement of experts on the practice of pharmaceutical care for cancer pain management in outpatient clinics. Objectives: This study aimed to use the Delphi consensus process to provide expert recommendations on the practice of cancer pain management in outpatient clinics from the point of view of pharmaceutical care in clinical practice and future clinical trials. Methods: A comprehensive literature review was conducted to draft the initial practice. In this process, 30-40 senior experts from various provinces in China were invited to rank the items of practice during the two Delphi consultations. The definitions of consensus included a combination with an average score of ≥4, the percentage of experts rating the scores at >4 points, and the coefficient of variation of the scores. Results: The expert panel comprised 18 pharmacists, 3 anesthesiologists, 6 oncologists, and 9 nurses. As a result of a comprehensive review, 33 items were initially formed. Among them, the consensus was reached for 27 items after the first Delphi round. The other six items and a total of five items for supplementation entered the second round, among which consensus was reached for eight items and three items were excluded. Expert consensus was achieved on 35 items after two rounds of consultation, which involved the collection of patient basic information, comprehensive pain assessment, breakthrough or neuropathic pain assessment, analgesic treatment evaluation, out-of-hospital follow-up, medical records, and evidence-based documents for reference. Conclusion: The final list of 35 items could be used to develop the practice of pharmaceutical care for cancer pain management in outpatient clinics in China. The practice may aid in the standardization of pharmaceutical care for pain, relieve pain to the greatest extent possible, and enhance the level of pain management in China.

Ongoing Clinical Trials in Aging-Related Tissue Fibrosis and New Findings Related to AhR Pathways.

Fibrosis is a pathological manifestation of wound healing that replaces dead/damaged tissue with collagen-rich scar tissue to maintain homeostasis, and complications from fibrosis contribute to nearly half of all deaths in the industrialized world. Ageing is closely associated with a progressive decline in organ function, and the prevalence of tissue fibrosis dramatically increases with age. Despite the heavy clinical and economic burden of organ fibrosis as the population ages, to date, there is a paucity of therapeutic strategies that are specifically designed to slow fibrosis. Aryl hydrocarbon receptor (AhR) is an environment-sensing transcription factor that exacerbates aging phenotypes in different tissues that has been brought back into the spotlight again with economic development since AhR could interact with persistent organic pollutants derived from incomplete waste combustion. In addition, gut microbiota dysbiosis plays a pivotal role in the pathogenesis of numerous diseases, and microbiota-associated tryptophan metabolites are dedicated contributors to fibrogenesis by acting as AhR ligands. Therefore, a better understanding of the effects of tryptophan metabolites on fibrosis modulation through AhR may facilitate the exploitation of new therapeutic avenues for patients with organ fibrosis. In this review, we primarily focus on how tryptophan-derived metabolites are involved in renal fibrosis, idiopathic pulmonary fibrosis, hepatic fibrosis and cardiac fibrosis. Moreover, a series of ongoing clinical trials are highlighted.

Phosphorylation of covalent organic framework nanospheres for inhibition of amyloid-ß peptide fibrillation.

The development and exploration of new nanostructural inhibitors against Alzheimer's disease (AD)-associated amyloid-ß (Aß) fibrillation have attracted extensive attention and become a new frontier in nanomedicine. However, focusing on finding an effective nanostructure is one of the most challenging parts of the therapeutics task. Herein, nanoscale spherical covalent organic frameworks (COFs) via post-synthetic functionalization with sodium phosphate (SP) groups on the channel networks were found to efficiently inhibit Aß fibrillation. The as-prepared uniform SP-COF nanospheres with high surface area, good crystallinity, and chemical stability were characterized by multifarious microscopic and spectroscopic techniques. Moreover, molecular dynamics simulation together with fibrillation kinetics and cytotoxicity assay experiments shows that there were restricted-access adsorption channels in the SP-COFs which were formed by the cavities with size and functional groups accommodated to the Aß peptide sequence and significantly affected the fibrillation and cytotoxicity of Aß. Transmission electron microscopy (TEM), dynamic light scattering (DLS) monitoring, isothermal titration calorimetry (ITC), Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra measurements, and confocal imaging observation were performed to understand the inhibition mechanism and influencing factors of the SP-COFs. To our knowledge, our strategy is the first exploration of COF-based anti-amyloidogenic nanomaterials with high affinity and specific targeting, which are crucial for the inhibition of Aß fibrillation for AD prevention and treatment.