Exploring the mechanism of Sendeng-4 against rheumacid arthritis through integrated serum pharmacochemistry, transcriptomics, and network pharmacology.

Mongolian medicine Sendeng-4 (SD-4) has demonstrated satisfactory clinical treatment outcomes for rheumatoid arthritis (RA); nevertheless, its bioactive components and the related mechanisms have not yet been clearly elucidated. To explore the bioactive chemical components of SD-4 in the treatment of RA and its possible mechanisms, an High Performance Liquid Chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to simultaneously quantify the main components in SD-4, and ultraperformance LC-Q-Exactive-MS/MS (UPLC-Q-Exactive-MS/MS) was used to identify the phytochemicals absorbed in the serum. Then, using network pharmacology methods, these components were constructed into a compound-target network of RA to predict possible biological targets of SD-4 as well as potential signaling pathways. Transcriptomics analysis and molecular docking were used to validate the results of network pharmacology. Subsequently, we established a complete Freund's adjuvant-induced RA rat model and observed the anti-RA effects of SD-4 through assessments of foot swelling, ankle diameter, arthritis score, morphology, serum inflammatory factors, and histopathological analysis of synovial tissue. Specifically, reverse transcription-quantitative polymerase chain reaction, Western blot, and immunohistochemical analysis were used in animal experiments to validate the pathways of serum phytochemistry, network pharmacology, and transcriptomics. Tannic acid, gallic acid, corilagin, crocin I, gardenoside, ferulic acid, quercetin, limonin, rutin, chlorogenic acid, verbascoside, catechin, epicatechin, myricetin, and dihydromyricetin in SD-4 showed good linearity within their respective concentration ranges (r ≥ 0.9991); the average recovery rate was 93.77%-109.17% (relative standard deviation < 2%). A total of 37 compounds were identified in serum samples. Based on this, network pharmacology methods collected 739 genes related to these identified compounds in SD-4 and 3807 genes related to RA. Network pharmacology and transcriptomic analysis demonstrated that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway is the most relevant pathway affected by SD-4 in RA. In the experiments, SD-4 treatment reduced ankle swelling and arthritis scores in RA rats, improved symptoms, and reduced the production of inflammatory factors. Compared with the RA model group, SD-4 treatment significantly reduced the expression of PI3K-Akt pathway-related messenger RNA and proteins. In addition, immunohistochemical analysis confirmed these results. This study combined serum phytochemistry, network pharmacology, and transcriptomics to demonstrate that SD-4 can alleviate RA by regulating the PI3K-Akt signaling pathway. This research provides a theoretical basis for the clinical application of SD-4 and offers an effective strategy for the identification of bioactive substances in traditional Chinese medicine formulas and the study of their potential mechanisms.

The Spanish Short Dark Tetrad (SD4): Association With Personality and Psychological Problems / El Cuestionario Corto de la Tétrada Oscura (SD4) en Español: Asociación con la Personalidad y los Problemas Psicológicos

Background: The Short Dark Tetrad (SD4) is a recently developed instrument for assessing the “dark” personality traits of psychopathy, narcissism, Machiavellianism, and sadism. We aimed to examine the SD4’s psychometric properties, adapting it into Spanish and exploring its structure, gender invariance, reliability, concurrent validity, and nomological network. Method: A sample of 668 adults (Mage = 26.36, SD = 10.64, 69.2% females) completed the SD4 and other self-report questionnaires. Results: The results demonstrated sound indices of reliability and concurrent validity, an adequate four-factor structure, and support for gender invariance. Furthermore, most of the findings about the nomological network were in line with prior hypotheses: All four SD4 scales were associated with low levels of agreeableness and antagonism; psychopathy was also related to low conscientiousness, disinhibition and impulse-control problems; narcissism was positively associated with extraversion and negatively associated with internalizing symptoms; Machiavellianism was uncorrelated with impulsivity- related problems, which made it distinct from the psychopathy profile; finally, sadism showed a similar pattern of associations to psychopathy, albeit less strongly linked to impulsivity problems and externalizing behavior. Conclusions: Overall, the SD4 presents sound psychometric properties, although the overlap between psychopathy and sadism warrants some caution.(AU)

Antecedentes: El Short Dark Tetrad (SD4) es un instrumento recientemente desarrollado para evaluar los rasgos “oscuros” de personalidad de psicopatía, narcisismo, maquiavelismo y sadismo. Nuestro objetivo fue profundizar en las propiedades psicométricas del SD4 adaptando el instrumento al español, y examinar su estructura, invariancia de género, fiabilidad, validez concurrente y red nomológica. Método: Una muestra de 668 adultos (Medad = 26,36, SD = 10,64, 69,2% mujeres) completaron el SD4 y otros cuestionarios. Resultados: Encontramos índices apropiados de fiabilidad y validez concurrente, una estructura de cuatro factores, y apoyo a la invariancia de género. Además, los hallazgos sobre la red nomológica estuvieron mayoritariamente en línea con las hipótesis prerregistradas: las cuatro escalas SD4 se asociaron con baja amabilidad y antagonismo; la psicopatía se relacionó con baja responsabilidad, desinhibición y problemas de impulsividad; el narcisismo se asoció con extraversión y negativamente con síntomas de interiorización; el maquiavelismo no correlacionó con problemas de impulsividad, por lo que mostró un perfil diferenciado al de psicopatía; el sadismo mostró un patrón de asociaciones similar a psicopatía, aunque menos vinculado a problemas de impulsividad y comportamientos externalizantes. Conclusiones: En general, el SD4 presenta buenas propiedades psicométricas, aunque el solapamiento entre psicopatía y sadismo justifica cierta precaución.(AU)

Whole-genome sequence of a putative pathogenic Bacillus sp. strain SD-4 isolated from cattle feed.

OBJECTIVES: The present study describes the draft genome sequence of a novel Bacillus sp. strain SD-4 isolated from animal feed. The study aims to get a deeper insight into antimicrobial resistance and secondary metabolite biosynthetic gene clusters (BGCs) and the association between them. METHODS: The strain SD-4 was preliminarily evaluated for antibacterial activities, motility, biofilm formation, and enterotoxin production using in vitro assays. The genome of strain SD-4 was sequenced using the Illumina HiSeq 2500 platform with paired-end reads. The reads were assembled and annotated using SPAdes and PGAP, respectively. The genome was further analysed using several bioinformatics tools, including TYGS, AntiSMASH, RAST, PlasmidFinder, VFDB, VirulenceFinder, CARD, PathogenFinder, MobileElement finder, IslandViewer, and CRISPRFinder. RESULTS: In vitro assays showed that the strain is motile, synthesises biofilm, and produces an enterotoxin and antibacterial metabolites. The genome analysis revealed that the strain SD-4 carries antimicrobial resistance genes (ARGs), virulence factors, and beneficial secondary metabolite BGCs. Further genome analysis showed interesting genome architectures containing several mobile genetic elements, including two plasmid replicons (repUS22 and rep20), five prophages, and at least four genomic islands (GIs), including one Listeria pathogenicity island LIPI-1. Moreover, the strain SD-4 is identified as a putative human pathogen. CONCLUSION: The genome of strain SD-4 harbours several BGCs coding for biologically active metabolites. It also contains antimicrobial resistance genes and is identified as a potential human pathogen. These results can be used to better comprehend antibiotic resistance in environmental bacteria that are not influenced by human intervention.

Complete Genomic Data of Enterobacter asburiae Strain SD4L Associated with Bacterial Palea Browning of Rice in China.

Enterobacter asburiae is the causal agent of rice bacterial palea browning disease. Here, we report the complete genome of E. asburiae strain SD4L, which represents the first whole genome sequence of an isolate from rice seedlings in China. The assembled genome consisted of two contigs, with a circular chromosome of 4,574,166 bp, and a plasmid of 85,271 bp, respectively. This complete genome will provide a valuable resource for further studies on bacterial palea browning worldwide.

Identification of the key amino acid sites of the carbendazim hydrolase (MheI) from a novel carbendazim-degrading strain Mycobacterium sp. SD-4.

A novel carbendazim (methyl-1H-benzimidazol-2-ylcarbamate, or MBC) degrading strain SD-4 was isolated and identified preliminarily as Mycobacterium sp. according to its phenotypic features and phylogenetic analysis. This strain could utilize MBC as the sole carbon and nitrogen sources for growth and degrade 50mgL-1 MBC at the average degradation rate of 0.63mgL-1h-1. Strain SD-4 degraded MBC through the typical pathway, in which MBC was first hydrolyzed by MheI to 2-aminobenzimidazole (2-AB) and then converted to 2-hydroxybenzimidazole (2-HB). The MBC hydrolase encoding gene mheI was cloned from strain SD-4 and successfully expressed in Escherichia coli by codon optimization. The sulfhydryl-blocking assay revealed that the activity of MheI was closely related to cysteine, and the site-directed mutation experiment showed that Cys16 and Cys222 played important roles during the hydrolysis of MBC by MheI. Therefore they affected its activity directly and were defined as the key amino acid sites.