DFT-based analysis of siderophore-metal ion interaction for efficient heavy metal remediation.

Siderophores have great application potential in metal pollutant remediation because of their effective cost and friendly impact on the environment. However, the practical use of siderophores in the remediation of specific metals is rather limited because of the weak nonspecific interactions between the siderophores and different metals. Thus, screening for a siderophore with optimal interaction with a specific metal would be necessary. In this study, the interaction between metal ions and moieties that donate the oxygen ligands for the coordination of four types of siderophore (hydroxamates, catecholates, phenolates, and carboxylates) was modeled and analyzed. As revealed by DFT-based analysis, the four types of siderophore generally exhibited selection preference for different metal ions in the order Ga3+ > Al3+ > Fe3+ > Cr3+ > Ni2+ > Cu2+ > Zn2+ > Co2+ > Mn2+ > Hg2+ > Pb2+ > Cd2+, which was determined mainly by the electronegativity of the siderophore functional groups, the electronegativity of the metals, and the ionic radius of the metals, as well as the interaction between the siderophores and the metals. Moreover, the effect of linear or nonlinear (cyclic) structure on the affinity of each siderophore for different metal ions was evaluated. In most situations, metal-bound cyclic siderophores were found to be more stable than their linear counterparts. Thus, proper siderophores for the remediation of metal pollution may be rapidly screened using this model.

Exosomal MiR-381 from M2-polarized macrophages attenuates urethral fibroblasts activation through YAP/GLS1-regulated glutaminolysis.

OBJECTIVE AND DESIGN: Post-traumatic urethral stricture is a clinical challenge for both patients and clinicians. Targeting glutamine metabolism to suppress excessive activation of urethral fibroblasts (UFBs) is assumed to be a potent and attractive strategy for preventing urethral scarring and stricture. MATERIAL OR SUBJECTS: In cellular experiments, we explored whether glutaminolysis meets the bioenergetic and biosynthetic demands of quiescent UFBs converted into myofibroblasts. At the same time, we examined the specific effects of M2-polarized macrophages on glutaminolysis and activation of UFBs, as well as the mechanism of intercellular signaling. In addition, findings were further verified in vivo in New Zealand rabbits. RESULTS: It revealed that glutamine deprivation or knockdown of glutaminase 1 (GLS1) significantly inhibited UFB activation, proliferation, biosynthesis, and energy metabolism; however, these effects were rescued by cell-permeable dimethyl α-ketoglutarate. Moreover, we found that exosomal miR-381 derived from M2-polarized macrophages could be ingested by UFBs and inhibited GLS1-dependent glutaminolysis, thereby preventing excessive activation of UFBs. Mechanistically, miR-381 directly targets the 3'UTR of Yes-associated protein (YAP) mRNA to reduce its stability at the transcriptional level, ultimately downregulating expression of YAP, and GLS1. In vivo experiments revealed that treatment with either verteporfin or exosomes derived from M2-polarized macrophages significantly reduced urethral stricture in New Zealand rabbits after urethral trauma. CONCLUSION: Collectively, this study demonstrates that exosomal miR-381 from M2-polarized macrophages reduces myofibroblast formation of UFBs and urethral scarring and stricture by inhibiting YAP/GLS1-dependent glutaminolysis.

Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis.

Background: Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive sensory neuropathy, was caused mainly by biallelic mutations in the NTRK1 gene. The pathogenesis of CIPA still needs further elucidation. Methods: Here, we recruited a CIPA case and introduced whole-exome sequencing (WES) to identify the causative variation. Subsequently, an in silico molecular dynamic (MD) analysis was performed to explore the intramolecular impact of the novel missense variant. Meanwhile, in vitro functional study on the novel variant from a metabolomic perspective was conducted via the liquid chromatography-mass spectrometry (LC-MS) approach, of which the result was verified by quantitative real-time PCR (qRT-PCR). Results: A novel compound heterozygous variation in NTRK1 gene was detected, consisting of the c.851-33T > A and c.2242C > T (p.Arg748Trp) variants. MD result suggested that p.Arg748Trp could affect the intramolecular structure stability. The results of the LC-MS and metabolic pathway clustering indicated that the NTRK1Arg748Trp variant would significantly affect the purine metabolism in vitro. Further analysis showed that it induced the elevation of NT5C2 mRNA level. Conclusion: The findings in this study extended the variation spectrum of NTRK1, provided evidence for counseling to the affected family, and offered potential clues and biomarkers to the pathogenesis of CIPA.

[Neurological Complications with Paraplegia as Main Manifestation after Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the cause, diagnosis and therapeutic method of the neurological complication with the main manifestation of paraplegia after the hematopoietic stem cell transplantation (HSCT). METHODS: The clinical features, the process of diagnosis and treatment and the prognosis follow-up of 9 cases, who received HSCT in our department during January 2014 and January 2017 and had the neurological complication with the main symptom of paraplegia after the transplantation, were summarized. RESULTS: The incidence rate of paraplegia was 2.96% (9/304). The median onset time was 245 days (50 days-772 days) after transplantation. The cause of paraplegia determined by examination was extramedullary recurrence of leukemia in 3 cases, cyclosporin neurotoxicity in 1 case, GBS in 1 case, CIDP in 2 cases and autoimmune myeleterosis in 2 cases. One patient abandoned the treatment. The rest 8 patients received empirical or targeted treatment. The median follow-up period was 11 months. There were 5 dead cases and 4 survival cases. CONCLUSION: Paraplegia is a serious post-HSCT complication. The cause of paraplegia should be determined as early as possible to perform targeted treatment. Empirical preemptive treatment should be given if necessary, so as to improve the survival rate and the quality of life of HSCT patients.

The association of different types of cerebral infarction with post-stroke depression and cognitive impairment.

The aim of this study was to investigate post-stroke depression (PSD) and cognitive impairments in patients with different types of cerebral infarction.A total of 110 patients with cerebral infarction treated in our hospital from January 2015 to February 2016 were included in present study. Forty-seven patients were PSD patients and 63 patients were non-PSD patients. The Hamilton Depression Rating Scale (HAMD) and Mini-Mental State Examination (MMSE) were employed to assess depression and cognition of patientsAmong PSD patients, the proportion of patients with partial anterior circulation infarction (PACI, 68.75%) was significantly higher than patients with lacunar circulation infarction (LACI, 29.17%) and posterior circulation infarction (POCI, 26.67%) (P < .05). No significant difference was found in PSD patients with LACI and POCI (P > .05). The MMSE score of patients with PACI (18.05 ±â€Š2.61) was lower than patients with POCI and LACI (P < .05), however, no significant difference was found in patients with LACI and POCI (P > 0.05). The incidences of cognitive impairment in patients with PACI, LACI, and POCI were 12.50%, 14.58%, and 13.33%, respectively. The MMSE score of PSD patients (21.23 ±â€Š2.12) was significantly lower than non-PSD patients (P < .05).Compared with LACI and POCI patients, PACI patients had a higher incidence of PSD and impaired cognitive functions. In addition, affective disorders such as depression may be correlated with cognitive impairment in patients with cerebral infarction.