Design, Synthesis, Antifungal Evaluation, Structure-Activity Relationship (SAR) Study, and Molecular Docking of Novel Spirotryprostatin A Derivatives.

Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.

The complete chloroplast genome sequences of an endemic species of Urticaceae (Debregeasia hekouensis).

Debregeasia hekouensis, which belongs to the nettle family (Urticaceae), is a local endemic species in Hekou County, Yunnan Province, China. To provide a basis for the development of effective molecular markers for its conservation, we sequenced the chloroplast (cp) genome of D. hekouensis in the present study. The total length of the chloroplast(cp) genome was 155,941 bp, and exhibited a typical quadripartite structure, with a pair of IRs (inverted repeats; 25,664 bp in length) being separated by a small single copy (SSC) region of 19,085 bp and a large single copy (LSC) region of 85,528 bp. The cp genome contained a total of 112 genes, including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. The GC content of the entire cp genome, LSC region, SSC region, and IR region was 36.3%, 34.0%, 29.4%, and 42.7%, respectively. Phylogenetic analysis indicated that D. hekouensis is evolutionarily closer to Debregeasia orientalis and Debregeasia squamata.

[Visual analysis of literature knowledge structure and acupoint matching rules of acupuncture for depression].

OBJECTIVE: To analyze the literature knowledge structure and acupoint matching rules of acupuncture for depression. METHODS: The articles regarding acupuncture for depression published from January 1 of 1984 to October 19 of 2020 were searched in CNKI database. CiteSpace5.7.R2 software was used to import the literature data, and the keyword cluster analysis, emergence analysis and time-zone analysis of articles and acupoints were conducted, and the map of scientific knowledge was draw. RESULTS: A total of 3524 articles were included to the knowledge structure analysis, while 601 articles into the acupoint matching rules analysis. There were 13 keyword clusters of acupuncture for depression, with "post-stroke depression" and "electroacupuncture treatment" as high-frequency keywords, and "electroacupuncture treatment" and "Hamilton depression scale" had high centrality, and "electroacupuncture treatment" had the highest emergence intensity. The keywords such as "electroacupuncture treatment" and "Hamilton depression scale", etc. appeared the earliest, followed by "post-stroke depression", "fluoxetine" and "auricular point therapy", etc. According to traditional Chinese medicine theory, acupoint keywords were divided into four clusters: ①core acupoint, ②replenishing-spleen and dispelling phlegm, dispersing-liver and relieving depression, reinforcing qi and nourishing blood, ③back-shu points, five-zhi points, ④inducing-resuscitation and opening-closes. CONCLUSION: The main knowledge structure of acupuncture for depression includes five parts: treatment method, depression type, TCM-related diseases, literature type and curative effect index. Clinical acupoint matching should adhere to the principle of "focusing the disease before syndrome" and "combination of disease and syndrome", and treatment should be modified for the syndromes of phlegm stagnation blocking, liver-stagnation and qi-stagnation, and deficiency of both qi and blood.

Interleukin-4 assisted calcium-strontium-zinc-phosphate coating induces controllable macrophage polarization and promotes osseointegration on titanium implant.

Titanium (Ti) and its alloys are believed to be promising scaffold materials for dental and orthopedic implantation due to their ideal mechanical properties and biocompatibility. However, the host immune response always causes implant failures in the clinic. Surface modification of the Ti scaffold is an important factor in this process and has been widely studied to regulate the host immune response and to further promote bone regeneration. In this study, a calcium-strontium-zinc-phosphate (CSZP) coating was fabricated on a Ti implant surface by phosphate chemical conversion (PCC) technique, which modified the surface topography and element constituents. Here, we envisioned an accurate immunomodulation strategy via delivery of interleukin (IL)-4 to promote CSZP-mediated bone regeneration. IL-4 (0 and 40 ng/mL) was used to regulate immune response of macrophages. The mechanical properties, biocompatibility, osteogenesis, and anti-inflammatory properties were evaluated. The results showed that the CSZP coating exhibited a significant enhancement in surface roughness and hydrophilicity, but no obvious changes in proliferation or apoptosis of bone marrow mesenchymal stem cells (BMMSCs) and macrophages. In vitro, the mRNA and protein expression of osteogenic related factors in BMMSCs cultured on a CSZP coating, such as ALP and OCN, were significantly higher than those on bare Ti. In vivo, there was no enhanced bone formation but increased macrophage type 1 (M1) polarization on the CSZP coating. IL-4 could induce M2 polarization and promote osteogenesis of BMMSCs on CSZP in vivo and in vitro. In conclusion, the CSZP coating is an effective scaffold for BMMSCs osteogenesis, and IL-4 presents the additional advantage of modulating the immune response for bone regeneration on the CSZP coating in vivo.

Introduction of ß-cyclodextrin into poly(aspartic acid) matrix for adsorption and time-release of ibuprofen.

Biodegradable copolymers with molecule inclusion ability was prepared by introduction of ß-cyclodextrin into poly(aspartic acid) matrices. The ibuprofen loading and dissolution properties of poly(aspartic acid)-ß-cyclodextrin were investigated.