Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) has become one of the leading causes of disa-bility and death in diabetic patients. Restoring blood supply to the hindlimbs, especially by promoting arteriogenesis, is currently the most effective strategy, in which endothelial cells play an important role. Tongxinluo (TXL) has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease. AIM: To investigate the effect of TXL on diabetic PAD and its underlying mechanisms. METHODS: An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice. Laser Doppler imaging and micro-computed tomography (micro-CT) were performed to assess the recovery of blood flow and arteriogenesis. Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology, Western blot analysis, enzyme-linked immuno-sorbent assay and real-time polymerase chain reaction assays. In vitro, human vascular endothelial cells (HUVECs) and human vascular smooth muscle cells (VSMCs) were pretreated with TXL for 4 h, followed by incubation in high glucose and hypoxia conditions to induce cell injury. Then, indicators of HUVEC pyroptosis and function, HUVEC-VSMC interactions and the migration of VSMCs were measured. RESULTS: Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis. TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway. In addition, TXL restored endothelial cell functions, including maintaining the balance of vasodilation, acting as a barrier to reduce inflammation, and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway. Similar results were observed in vitro. CONCLUSION: TXL has a pro-arteriogenic effect in the treatment of diabetic PAD, and the mechanism may be related to the inhibition of endothelial cell pyroptosis, restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.

Molecular characterization and functional analysis of IL-18 in snakehead (Channa argus) during Aeromonas schubertii and Nocardia seriolae infections.

As a proinflammatory cytokine of the interleukin-1 (IL-1) family, IL-18 plays important roles in host protection against bacterial, viral, and fungal infection. We cloned the open reading frame of snakehead (Channa argus) IL-18 (shIL-18) and found that it contained 609 base pairs and encoded 202 amino acid residues. The shIL-18 included a conserved IL-1-like family signature and two potential IL-1ß-converting enzyme cutting sites; one was conserved in all analyzed IL-18s, but the other was unique to shIL-18. Unlike other IL-18s, shIL-18 also contained a predicted signal peptide. In this study, shIL-18 was constitutively expressed in all tested tissues, and its expression was induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo and by lipoteichoic acid, lipopolysaccharides, and polyinosinic-polycytidylic acid in head kidney leukocytes in vitro. Moreover, recombinant shIL-18 upregulated the expression of interferon-γ, IL-1ß, and tumor necrosis factor-α1 and -α2 and promoted the proliferation of leukocytes. Taken together, these results showed that IL-18 played crucial roles in host defense against bacterial infection in fish, as it does in mammals.

Defective mitochondrial function by mutation in THICK ALEURONE 1 encoding a mitochondrion-targeted single-stranded DNA-binding protein leads to increased aleurone cell layers and improved nutrition in rice.

Cereal endosperm comprises an outer aleurone and an inner starchy endosperm. Although these two tissues have the same developmental origin, they differ in morphology, cell fate, and storage product accumulation, with the mechanism largely unknown. Here, we report the identification and characterization of rice thick aleurone 1 (ta1) mutant that shows an increased number of aleurone cell layers and increased contents of nutritional factors including proteins, lipids, vitamins, dietary fibers, and micronutrients. We identified that the TA1 gene, which is expressed in embryo, aleurone, and subaleurone in caryopses, encodes a mitochondrion-targeted protein with single-stranded DNA-binding activity named OsmtSSB1. Cytological analyses revealed that the increased aleurone cell layers in ta1 originate from a developmental switch of subaleurone toward aleurone instead of starchy endosperm in the wild type. We found that TA1/OsmtSSB1 interacts with mitochondrial DNA recombinase RECA3 and DNA helicase TWINKLE, and downregulation of RECA3 or TWINKLE also leads to ta1-like phenotypes. We further showed that mutation in TA1/OsmtSSB1 causes elevated illegitimate recombinations in the mitochondrial genome, altered mitochondrial morphology, and compromised energy supply, suggesting that the OsmtSSB1-mediated mitochondrial function plays a critical role in subaleurone cell-fate determination in rice.

The Impact of Mortality Salience on Purchase Intention and Creativity Evaluation on Products During COVID-19 Pandemic.

In the environment of COVID-19, people are faced with mortality salience (MS) and socioeconomic crisis. According to the terror management theory, the MS would lead to particular consumption attitudes and behaviors caused by the self-esteem and cultural worldview defense. The creativity as a potential value of products needs to be examined to explore how the MS changed the creativity evaluation of three types of products categorized into normal, renovative, and innovative products, based on the degree of originality (Zhang et al., 2019). Two experiments were conducted to examine (1) the MS effect on the creativity and purchase intention evaluation and (2) both MS and country-of-origin effect on the evaluations. The results show that usefulness and purchase intention are affected by both effects, and the novelty is mainly affected by MS.

Marinagarivorans algicola gen. nov., sp. nov., isolated from marine algae.

Two novel agar-degrading, Gram-stain-negative, motile, heterotrophic, facultatively anaerobic and pale yellow-pigmented bacterial strains, designated Z1T and JL1, were isolated from marine algae Gelidium amansii (Lamouroux) and Gracilaria verrucosa, respectively. Growth of the isolates was optimal at 28-30 °C, pH 7.0-7.5 and with 2-3 % (w/v) NaCl. Both strains contained Q-8 as the sole respiratory quinone. The major cellular fatty acids in strain Z1T were C18 : 1ω7c, C16 : 0 and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The predominant polar lipids in strain Z1T were phosphatidylethanolamine, phosphatidylglycerol and an aminolipid. The genomic DNA G+C content of both strains was 45.1 mol%. Strains Z1T and JL1 were closely related, with 99.9 % 16S rRNA gene sequence similarity. The average nucleotide identity (ANI) value between strains Z1T and JL1 was 99.3 %. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains Z1T and JL1 form a distinct phyletic line within the class Gammaproteobacteria, with less than 92.3 % similarity to their closest relatives. Based on data from the current polyphasic study, the isolates are proposed to belong to a novel species of a new genus designated Marinagarivorans algicola gen. nov., sp. nov. The type strain of the type species is Z1T ( = ATCC BAA-2617T = CICC 10859T).

Catenovulum maritimus sp. nov., a novel agarolytic gammaproteobacterium isolated from the marine alga Porphyra yezoensis Ueda (AST58-103), and emended description of the genus Catenovulum.

A novel agarolytic, Gram-stain negative, heterotrophic, facultatively anaerobic and pale-white pigmented bacterial strain, designated Q1(T), was isolated from the marine alga Porphyra yezoensis Ueda (AST58-103) collected from the coastal area of Weihai, China. The cells are motile by means of peritrichous flagella. The isolate requires NaCl for growth, while seawater is not necessary, and growth occurs optimally at about 30-33 °C, in 1-3 % (w/v) NaCl and at pH 7-7.5. Strain Q1(T) shows oxidase-positive and catalase-negative activities, and possesses the ability to hydrolyse starch and alginate, but not cellulose, gelatin, urea or Tween-80. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain Q1(T) is affiliated with the family Alteromonadaceae within the class Gammaproteobacteria. The isolate, strain Q1(T), is most closely related to Catenovulum agarivorans YM01(T) (94.85 %), with less than 91.2 % sequence similarity to other close relatives with validly published names. The draft genome sequence of strain Q1(T) consists of 62 contigs (>200 bp) of 4,548,270 bp. The genomes of Q1(T) and YM01(T) have an ANI value of 70.7 %, and the POCP value between the two genomes is 64.4 %. The genomic DNA G+C content of strain Q1(T) is 37.9 mol% as calculated from the draft genome sequence. The main isoprenoid quinone is ubiquinone-8. The predominant cellular fatty acids are summed feature 3 (C16:1 ω7c and/or iso-C15:0 2-OH), C16:0 and C18:1 ω7c. The major polar lipids are phosphatidylethanolamine and phosphatidylglycerol. Based on data from a polyphasic chemotaxonomic, physiological and biochemical study, strain Q1(T) should be classified as a novel species of the genus Catenovulum, for which the name Catenovulum maritimus sp. nov. is proposed. The type strain is Q1(T) (=CICC 10836(T)=DSM 28813(T)).