Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF-κB Activation and Protects against Inflammatory Responses.

The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is critical for cancer cell proliferation and immune cell phenotypes, but whether it can contribute to macrophage inflammatory responses remains unclear. In this study, we show that MTHFD2 was upregulated by LPS in murine macrophages upon activation of the TLR4-MyD88-IKKα/ß-NF-κB signaling pathway. MTHFD2 significantly attenuated LPS-induced macrophage proinflammatory cytokine production through its enzymatic activity. Notably, ablation of myeloid MTHFD2 rendered mice more sensitive to septic shock and CCl4-induced acute hepatitis. Mechanistically, MTHFD2 restrained IKKα/ß-NF-κB activation and macrophage inflammatory phenotype by scavenging reactive oxygen species through the generation of NADPH. Our study reveals MTHFD2 as a "self-control" mechanism in macrophage-mediated inflammatory responses.

Comprehensive nursing intervention improves quality of life and reduces hospitalization time and expense in elderly patients with severe heart failure undergoing rh-BNP treatment.

OBJECTIVE: This study was designed to explore the efficacy of comprehensive nursing intervention in elderly patients with severe heart failure (SHF) treated by recombinant human brain natriuretic peptide (rh-BNP). METHODS: A retrospective analysis was made on 131 patients with SHF treated with rh-BNP in Wuhan Asia Cardiology Hospital from May 2019 to May 2022. Of them, 71 patients who received routine nursing care between May 2019 and December 2021 were assigned to the control group, and 60 patients who received comprehensive nursing between January 2022 and May 2022 were assigned to the observation group. The changes in quality of life (QoL) before and after nursing and the occurrence of adverse events after nursing were counted and compared between the two groups. The two groups were compared reagarding changes in anxiety and depression scores before and after nursing, as well as hospitalization expenses and hospitalization time. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) of patients were determined. The nursing satisfaction of the two groups was evaluated. Additionally, logistic regression was carried out to analyze the risk factors for adverse events. RESULTS: The control group had lower QoL scores than the observation group after nursing (P < 0.0001). The control group got significantly higher self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores than the observation group (P < 0.0001). The control group showed lower levels of LVEDV and LVEF than the observation group (P < 0.0001). The control group experienced greatly longer hospitalization time than the observation group, and also had a higher hospitalization expense than the observation group (P < 0.001). The observation group expressed much higher nursing satisfaction than the control group (P=0.007). Additionally, according to multivariate logistic regression analysis, age, hypertension, and diabetes mellitus were independent risk factors for adverse events (P < 0.05). CONCLUSION: For elderly SHF patients treated by rh-BNP, comprehensive nursing intervention can contribute to higher QoL, shorter hospitalization time, lower hospitalization expense, and milder negative emotions, but did not correlate with short-term adverse cardiovascular events.

Novel insights on genes and pathways involved in Pinus elliottii response to resinosis.

Pinus elliottii, an important coniferous timber species, has recently become one of the most popular sources of resin in China. Resinosis is a common disease that may negatively affect pine tree growth and production. In this study, we used single-molecule real-time sequencing and Illumina RNA sequencing to generate an accurate transcriptome for P. elliottii. The transcriptome included 90,026 transcripts, 5160 long non-coding RNAs and 7710 transcription factors. We then analyzed RNA-sequencing, small RNA-sequencing and degradome data to identify genes, miRNAs and key miRNA-target pairs involved in response to resinosis in P. elliottii. We identified 1305 genes and 1151 miRNAs exhibiting significant differential expression in response to resinosis. According to the degradome sequencing analysis, 318 differentially expressed transcripts were targets of 14 differentially expressed miRNAs. Our study has provided resources for further functional characterization of genes and miRNAs involved in resinosis in P. elliottii, which should aid the future disease-resistance breeding of this species.

Extensive genomic plasticity in Pseudomonas aeruginosa revealed by identification and distribution studies of novel genes among clinical isolates.

The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.