Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling.

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

A comparison of Mersilene tape versus braided suture in transvaginal cervical cerclage: A retrospective case-control study.

OBJECTIVE: Previous studies have indicated that there is an association between cervical cerclage and type of suture material. However, it is still unclear which suture material can provide the greatest benefit to patients who have undergone cerclage. This study investigated the effect of two different suture materials (Mersilene tape vs braided suture) used for transvaginal cervical cerclage placement on maternal outcomes of women with cervical insufficiency. METHODS: In this retrospective case-control study, 170 women who underwent history-, ultrasound-, or physical examination-indicated transvaginal cervical cerclage were categorized according to suture materials used for cerclage: a total of 96 received Mersilene tape and 74 received braided suture. Study participants received a transvaginal cervical cerclage before 28 weeks and were followed up until delivery to assess pregnancy and neonatal outcomes. The primary outcome was gestational age at delivery. Secondary outcomes included preterm premature rupture of membranes (PPROM), premature rupture of membranes (PROM), chorioamnionitis, neonatal survival rate, and neonatal morbidity. RESULTS: Out of 170 eligible women, 74 (43.5%) received braided suture while 96 (56.5%) received Mersilene tape. Baseline characteristics were similar between the two groups. The group that received braided suture had a lower incidence of gestational age at delivery <37 weeks (29.2% vs 54.2%, P = 0.046), PPROM (9.5% vs 21.9%, P = 0.029) and PROM (17.6% vs 32.3%, P = 0.028) compared to the group that received Mersilene tape. However, there were no significant differences between the two groups in average gestational age at delivery, the rate of gestational age at delivery <24, <28, <32, and < 34 weeks, chorioamnionitis, and neonatal survival rate, as well as neonatal morbidity. CONCLUSION: Compared to Mersilene tape, the utilization of braided suture has been significantly associated with a reduction in the incidence of gestational age at delivery <37 weeks, as well as a decreased risk of PPROM and PROM. However, the use of braided sutures did not result in discernible differences in the rates of chorioamnionitis or adverse neonatal outcomes.

Using kin discrimination to construct synthetic microbial communities of Bacillus subtilis strains impacts the growth of black soldier fly larvae.

Using synthetic microbial communities to promote host growth is an effective approach. However, the construction of such communities lacks theoretical guidance. Kin discrimination is an effective means by which strains can recognize themselves from non-self, and construct competitive microbial communities to produce more secondary metabolites. However, the construction of cooperative communities benefits from the widespread use of beneficial microorganisms. We used kin discrimination to construct synthetic communities (SCs) comprising 13 Bacillus subtilis strains from the surface and gut of black soldier fly (BSF) larvae. We assessed larval growth promotion in a pigeon manure system and found that the synthetic community comprising 4 strains (SC 4) had the most profound effect. Genomic analyses of these 4 strains revealed that their complementary functional genes underpinned the robust functionality of the cooperative synthetic community, highlighting the importance of strain diversity. After analyzing the bacterial composition of BSF larvae and the pigeon manure substrate, we observed that SC 4 altered the bacterial abundance in both the larval gut and pigeon manure. This also influenced microbial metabolic functions and co-occurrence network complexity. Kin discrimination facilitates the rapid construction of synthetic communities. The positive effects of SC 4 on larval weight gain resulted from the functional redundancy and complementarity among the strains. Furthermore, SC 4 may enhance larval growth by inducing shifts in the bacterial composition of the larval gut and pigeon manure. This elucidated how the SC promoted larval growth by regulating bacterial composition and provided theoretical guidance for the construction of SCs.

Microbial mechanisms in nitrogen fertilization: Modulating the re-mobilization of clay mineral-bound cadmium in agricultural soils.

Soil cadmium (Cd) can affect crop growth and food safety, and through the enrichment in the food chain, it ultimately poses a risk to human health. Reducing the re-mobilization of Cd caused by the release of protons and acids by crops and microorganisms after stabilization is one of the significant technical challenges in agricultural activities. This study aimed to investigate the re-mobilization of stabilized Cd within the clay mineral-bound fraction of soil and its subsequent accumulation in crops utilizing nitrogen ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N), at 60 and 120 mg kg-1. Furthermore, the study harvested root exudates at various growth stages to assess their direct influence on the re-mobilization of stabilized Cd and to evaluate the indirect effects mediated by soil microorganisms. The results revealed that, in contrast to the NO3--N treatment, the NH4+-N treatment significantly enhanced the conversion of clay mineral-bound Cd in the soil to NH4NO3-extractable Cd. It also amplified the accumulation of Cd in edible amaranth, with concentrations in roots and shoots rising from 1.7-6.0 mg kg-1 to 4.3-9.8 mg kg-1. The introduction of NH4+-N caused a decrease in the pH value of the rhizosphere soil and stimulated the production and secretion organic and amino acids, such as oxalic acid, lactic acid, stearic acid, succinic acid, and l-serine, from the crop roots. Furthermore, compared to NO3--N, the combined interaction of root exudates with NH4+-N has a more pronounced impact on the abundance of microbial genes associated with glycolysis pathway and tricarboxylic acid cycle, such as pkfA, pfkB, sucB, sucC, and sucD. The effects of NH4+-N on crops and microorganisms ultimately result in a significant increase in the re-mobilization of stabilized Cd. However, the simulated experiments showed that microorganisms only contribute to 3.8-6.6 % of the re-mobilization of clay mineral-bound Cd in soil. Therefore, the fundamental strategy to inhibit the re-mobilization of stabilized Cd in vegetable cultivation involves the regulation of proton and organic acid secretion by crops.