Penta­carbonyl-1κ2 C,2κ3 C-(μ-pyrazine-2,3-dithiol­ato-1:2κ4 S,S′:S,S′)(trimethyl­phosphane-1κP)diiron(I)(Fe—Fe)

In the title compound, [Fe2(C4H2N2S2)(C3H9P)(CO)5], the Fe2S2 core adopts a butterfly conformation. The PMe3 ligand is coordinated in the basal position, roughly cis to the Fe—Fe bond. The Fe—Fe distance of 2.4970 (6) Å is relatively short compared to those (ca 2.53 Å) found in another monosubstituted diiron compound. A rigid planar dithiol­ate bridge is featured, with an angle of 2.78 (1)° between the Fe—Fe bond and the normal to the pyrazine-2,3-dithiol­ate plane

Local infiltration analgesia versus femoral nerve block in total knee arthroplasty: A meta-analysis

AbstractIntroductionLocal infiltration analgesia (LIA) and femoral nerve block (FNB) are both used for the pain management after total knee arthroplasty (TKA). Controversy still remains regarding the optimal technique for pain relief in patients undergoing TKA. The purpose of this meta-analysis was to compare the analgesia achieved with LIA and the one from FNB following TKA.HypothesisLIA achieves better pain control than FNB in patients with TKA.MethodsDatabases, including Pubmed, EMBASE, the Cochrane Library and Web of Science were comprehensively searched to identify studies comparing LIA with FNB for patients with TKA. Two reviewers independently selected trials, extracted data, and assessed the methodological qualities of included studies. Data were analyzed by RevMan 5.2.ResultsNine RCTs involving 782 patients were included. LIA achieved more rapid pain relief (VAS) at 6h postoperatively [SMD6h=−0.92, 95% CI (−1.38, −0.47)] than FNB. There were no significant differences at 24h and 48h [SMD24h=−0.03, 95% CI (−0.46, 0.40); SMD48h=0.28, 95% CI (−0.35, 0.91)], VAS with activity at 24h and 48h [SMD6h=−0.54, 95% CI (−1.62, 0.54); SMD24h=−0.22, 95% CI (−1.41, 0.96); SMD48h=−0.08, 95% CI (−0.52, 0.69)], opioid consumption at 24h and 48h [SMD24h=−0.24, 95% CI (−0.82, 0.34); SMD48h=0.15, 95% CI (0.25, 0.54)] and length of hospital stay [MD=−0.52, 95% CI (−1.13, 0.09)].DiscussionLIA may be the better choice in the pain management of TKA for it could achieve fast pain relief and is easier to perform than FNB for patients with TKA.Level of evidenceLevel II, meta-analysis and systematic review

Multiple compounds determination and fingerprint analysis of herbal preparation Shuang-Huang-Lian capsule by HPLC-DAD

The objective of this paper was to develop a high performance liquid chromatography with diode array detection both for chromatographic fingerprint and simultaneous determination of twelve analytes of Shuang-Huang-Lian (SHL) capsule. The chromatographic separation was performed on an Aglient Zorbax SB-C18 column with a gradient elution program using a mixture of acetonitrile and 0.2 % acetic acid as mobile phase within 110 min detected at 278 nm wavelength. For fingerprint analysis, 50 peaks were selected as the common peaks to evaluate the similarities of different samples collected from different pharmaceutical companies in China, and two kinds of data, relative retention time and relative peak area were used to identify the common peaks in samples for investigation. SHL capsules from different batches of the same manufacturer or different manufacturers showed a close similarity. For quantitative analysis, linear regressions, limit of detection and quantification, intra-day and inter-day precisions, recovery, repeatability and stability were all tested and good results were obtained to simultaneously determine the 12 marker compounds in the samples. The validated method coupled with multiple compounds determination and fingerprint analysis is a powerful and meaningful tool to comprehensively conduct the quality control of TCM.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Retrotransposition creates sloping shores: a graded influence of hypomethylated CpG islands on flanking CpG sites

Long interspersed elements (LINEs), through both self-mobilization and trans-mobilization of short interspersed elements and processed pseudogenes, have made an indelible impact on the structure and function of the human genome. One consequence is the creation of new CpG islands (CGIs). In fact, more than half of all CGIs in the genome are associated with repetitive DNA, three-quarters of which are derived from retrotransposons. However, little is known about the epigenetic impact of newly inserted CGIs. We utilized a transgenic LINE-1 mouse model and tracked DNA methylation dynamics of individual germline insertions during mouse development. The retrotransposed GFP marker sequence, a strong CGI, is hypomethylated in male germ cells but hypermethylated in somatic tissues, regardless of genomic location. The GFP marker is similarly methylated when delivered into the genome via the Sleeping Beauty DNA transposon, suggesting that the observed methylation pattern may be independent of the mode of insertion. Comparative analyses between insertion- and non-insertion-containing alleles further reveal a graded influence of the retrotransposed CGI on flanking CpG sites, a phenomenon that we described as "sloping shores." Computational analyses of human and mouse methylomic data at single-base resolution confirm that sloping shores are universal for hypomethylated CGIs in sperm and somatic tissues. Additionally, the slope of a hypomethylated CGI can be affected by closely positioned CGI neighbors. Finally, by tracing sloping shore dynamics through embryonic and germ cell reprogramming, we found evidence of bookmarking, a mechanism that likely determines which CGIs will be eventually hyper- or hypomethylated

Contribution of basal ganglia activity to REM sleep disorder in Parkinson’s disease

Background: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson’s disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD. Method: Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD. Basal ganglia oscillatory patterns during RBD and REM sleep without atonia were analysed and compared with another age-matched cohort of patients with dystonia that served as controls. Results: We found that beta power in both basal ganglia nuclei was specifically elevated during REM sleep without atonia in patients with PD, but not in dystonia. Basal ganglia beta power during REM sleep positively correlated with the extent of atonia loss, with beta elevation preceding the activation of chin electromyogram activities by ~200 ms. The connectivity between basal ganglia beta power and chin muscular activities during REM sleep was significantly correlated with the clinical severity of RBD in PD. Conclusions: These findings support that basal ganglia activities are associated with if not directly contribute to the occurrence of RBD in PD. Our study expands the understanding of the role basal ganglia played in RBD and may foster improved therapies for RBD by interrupting the basal ganglia-muscular communication during REM sleep in PD

Effect of bioaugmentation on gas production and microbial community during anaerobic digestion in a low-temperature fixed-bed reactor

Low temperature is one of the limiting factors for anaerobic digestion in cold regions. To improve the efficiency of anaerobic digestion for methane production in stationary reactors under low-temperature conditions, and to improve the structure of the microbial community for anaerobic digestion at low temperatures. We investigated the effects of different concentrations of exogenous Methanomicrobium (10, 20, 30%) and different volumes of carbon fiber carriers (0, 10, 20%) on gas production and microbial communities to improve the performance of low-temperature anaerobic digestion systems. The results show that the addition of 30% exogenous microorganisms and a 10% volume of carbon fiber carrier led to the highest daily (128.15 mL/g VS) and cumulative (576.62 mL/g VS) methane production. This treatment effectively reduced the concentrations of COD and organic acid, in addition to stabilizing the pH of the system. High-throughput sequencing analysis revealed that the dominant bacteria under these conditions were Acidobacteria and Firmicutes and the dominant archaea were Candidatus_Udaeobacter and Methanobacterium. While the abundance of microorganisms that metabolize organic acids was reduced, the functional abundance of hydrogenophilic methanogenic microorganisms was increased. Therefore, the synergistic effect of Methanomicrobium bioaugmentation with carbon fiber carriers can significantly improve the performance and efficiency of low-temperature anaerobic fermentation systems

An Arrayed Genome-Wide Perturbation Screen Identifies the Ribonucleoprotein hnRNP K As Rate-Limiting for Prion Propagation

A defining characteristic of mammalian prions is their capacity for self-sustained propagation. Theoretical considerations and experimental evidence suggest that prion propagation is modulated by cell-autonomous and non-autonomous modifiers. Using a novel quantitative phospholipase protection assay (QUIPPER) for high-throughput prion measurements, we performed an arrayed genome-wide RNA interference (RNAi) screen aimed at detecting modifiers of prion propagation. We exposed prion-infected cells in high-density microplates to 35’364 ternary pools of 52’746 siRNAs targeting 17’582 genes representing the mouse protein-coding transcriptome. We identified 1191 modulators of prion propagation. While 1151 of these modified the expression of both the pathological prion protein, PrP$^{Sc}$, and its cellular counterpart PrP$^{C}$, 40 genes affected selectively PrP$^{Sc}$. Of the latter, 20 genes augmented prion production when suppressed. A prominent limiter of prion propagation was the heterogeneous nuclear ribonucleoprotein Hnrnpk. Psammaplysene A (PSA), which binds Hnrnpk, reduced prion levels in cultured cells and protected them from cytotoxicity. PSA also reduced prion levels in infected cerebellar organotypic slices and alleviated locomotor deficits in prion-infected Drosophila melanogaster expressing ovine PrP$^{C}$. Hence, genome-wide QUIPPER-based perturbations can discover actionable cellular pathways involved in prion propagation. Finally, the unexpected identification of a prioncontrolling ribonucleoprotein suggests a role for RNA in the generation of infectious prions

NF-κB Induced the Donor Liver Cold Preservation Related Acute Lung Injury in Rat Liver Transplantation Model

We have observed at our clinical work that acute lung injury (ALI) often occurs in patients transplanted with donor livers persevered for long time. So, we conducted this study to investigate the influence of cold preservation time (CPT) of donor liver on ALI induced by liver transplantation (LT), and further study the role of nuclear factor-κB (NF-κB) in the process.Wistar rats were used as donors and recipients to establish orthotopic rat liver transplantation models. Donor livers were preserved at 4°C for different lengths of time. The effect of NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC), on ALI was detected. All samples were harvested after 3 h reperfusion. The severity of liver injury was evaluated first. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue and liver outflow serum were measured respectively. The severity indexes of ALI, the activity of NF-κB and inhibitor-κBα (I-κBα) in lung/liver were measured accordingly.With the prolonged liver CPT, the liver damage associated indexes and ALI-related indexes all increased significantly. TNF-α and IL-1β in liver outflow serum increased accordingly, and the activity of NF-κB in liver/lung increased correspondingly. All these ALI-associated indexes could be partially reversed by the use of PDTC.Extended CPT aggravates the damage of donor liver and induces the expressions of TNF-α and IL-1β in liver. These inflammatory factors migrate to lung via liver outflow blood and activate NF-κB in lung, inducing ALI finally. NF-κB may play a critical role in LT-related ALI. Patients with or at risk of ALI may benefit from acute anti-inflammatory treatment with PDTC