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关键词： lung transplantation   ex vivo lung perfusion   cell-free DNA   primary graft dysfunction  

摘要： Background: Cell-free DNA (cfDNA), such as mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA), are known to be released from injured cells and as such have been explored as biomarkers for tissue injury in different clinical settings. Ex vivo lung perfusion (EVLP) has been developed as an effective technique for marginal donor lung functional assessment. We hypothesized that the level of cfDNA in EVLP perfusate may reflect tissue injury and thus can be developed as a biomarker to quantify the degree of donor lung injury or predict the development of primary graft dysfunction (PGD) after lung transplantation (LTx). Methods: The perfusate from 62 donor lungs transplanted at our institution between May 2010 and December 2015 was sampled for cfDNA at 1 and 4 hours of perfusion. Sequences of genes encoding nicotinamide adenine dinucleotide dehydrogenase 1 (NADH-1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were used to represent mtDNA and nuDNA, respectively. Levels were quantified by real-time polymerase chain reaction and correlated with clinical outcome after LTx. Results: In our entire cohort, 14 patients developed PGD grade 3 (PGD3) within 72 hours after LTx. The non-PGD group included 48 patients (PGD0-1). Concentrations of mtDNA in the perfusate of the PGD3 group were significantly higher than those in non-PGD group at 1 hour of EVLP (1874 +/- 844 vs 1259 +/- 885 copies/mu L;P = .011). The perfusate of the PGD3 group had significantly higher levels of nuDNA compared with the non-PGD group at both 1 hour (1498 +/- 1895 vs 675 +/- 391 copies/mu L;P = .008) and 4 hours (4521 +/- 5810 vs 1764 +/- 1494 copies/mu L;P = .001). In donation after cardiac death (DCD) cases, mtDNA levels were significantly higher in the PGD3 group compared with the non-PGD group at 1 hour of EVLP (2060 +/- 997 vs 1184 +/- 782 copies/mu L;P = .040), and the levels of nuDNA were significantly higher in the PGD3 group compared with the non-PGD group at both 1 hour (1021 +/- 495 vs 606 +

摘要： Male infertility impacts millions of couples yet, the etiology of primary infertility remains largely unknown. A critical element of successful spermatogenesis is maintenance of genome integrity. Here, we present a genomic study of spermatogenic failure (SPGF). Our initial analysis (n = 176) did not reveal known gene-candidates but identified a potentially significant single-nucleotide variant (SNV) in X-linked germ-cell nuclear antigen (GCNA). Together with a larger follow-up study (n = 2049), 7 likely clinically relevant GCNA variants were identified. GCNA is critical for genome integrity in male meiosis and knockout models exhibit impaired spermatogenesis and infertility. Single-cell RNA-seq and immunohistochemistry confirm human GCNA expression from spermatogonia to elongated spermatids. Five identified SNVs were located in key functional regions, including N-terminal SUMO-interacting motif and C-terminal Spartan-like protease domain. Notably, variant ***115ProfsTer7 results in an early frameshift, while Spartan-like domain missense variants ***659Trp and ***664Cys change conserved residues, likely affecting 3D structure. For variants within GCNA's intrinsically disordered region, we performed computational modeling for consensus motifs. Two SNVs were predicted to impact the structure of these consensus motifs. All identified variants have an extremely low minor allele frequency in the general population and 6 of 7 were not detected in > 5000 biological fathers. Considering evidence from animal models, germ-cell-specific expression, 3D modeling, and computational predictions for SNVs, we propose that identified GCNA variants disrupt structure and function of the respective protein domains, ultimately arresting germ-cell division. To our knowledge, this is the first study implicating GCNA, a key genome integrity factor, in human male infertility.

关键词： Crystal structure   Citrate synthase   Hymenobacter sp   PAMC 26554   Domain movement   X-ray crystallography  

摘要： Citrate synthase (CS) catalyzes the formation of citrate and coenzyme A from acetyl-CoA and oxaloacetate. CS exists in two forms: type I and type II. We determined the citrate-bound crystal structure of type II CS from the Hymenobacter sp. PAMC 26554 bacterium (HyCS;isolated from Antarctic lichen). Citrate molecules bound to a cleft between the large and small domains of HyCS. Structural comparison of HyCS with other type II CSs revealed that type II CSs have a highly conserved flexible hinge region (residues G264-P265 in HyCS), enabling correct positioning of active site residues. Notably, the catalytic His266 residue of HyCS interacted with Trp262 in the inactive (unliganded open) state of other type II CSs, whereas the His266 residue moved to the active site via a small-domain swing motion, interacting with the bound citrate in the closed conformation of HyCS. However, type I CSs lack this tryptophan residue and face-to-edge interactions. Thus, type II CSs might have a unique domain-motion control mechanism enabling a tight allosteric regulation. An activity assay using a W262A mutant showed a Hill coefficient of 2.4;thus, the interaction between Trp262 and His266 was closely related to the positive cooperative ligand binding of type II CS. (c) 2021 Published by Elsevier B.V.

摘要： Objective. To investigate the clinical effect of iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer and the effect on peripheral blood Th1/Th2 cells. Methods. A total of 136 patients with primary liver cancer from April 2017 to June 2018 were selected as subjects and randomly divided into the control group and observation group with 68 cases in each group. The control group was treated with chemotherapy, and the observation group was treated with iodine-125 seed implantation on the basis of the control group. After 3 months of treatment, the curative effect was investigated. Serum tumor markers, peripheral blood Th1/Th2 cells, and side effects and recurrence rate were compared between the two groups. Results. The levels of serum tumor markers in both groups at 3 months after treatment were lower than before treatment (P<0.05). Three months after treatment, the levels of tumor markers AFP, AFP-L3, and GP73 in the observation group were 14.61 +/- 3.49 mu g/L, 3.29 +/- 0.41 ng/mL, and 51.24 +/- 4.51 mu g/L, respectively, which were lower than those in the control group, 32.53 +/- 4.59 mu g/L, 5.63 +/- 0.63 ng/mL, and 71.52 +/- 6.05 mu g/L (P<0.05). At 3 months after treatment, the level of including interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) in Th1 cells of the observation group was higher than that of the control group (P<0.05), whereas the levels of IL-4, IL-6, and IL-10 in Th2 cells were lower than those in the control group (P<0.05). There was no statistical significance in the incidence of leukopenia, thrombocytopenia, and gastrointestinal reactions between the two groups (P>0.05). The recurrence rate of the observation group at 12, 24, and 36 months after treatment was lower than that of the control group (P<0.05). Conclusion. Iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer can reduce the level of serum tumor markers, improve the level of peripheral bloo

关键词： 装配式建筑   立面   设计   探讨  

摘要： 近年来,装配式建筑建造技术在中国快速发展,急于求成的发展模式使装配式建筑的立面效果较为呆板且单调,导致了对城市建筑风貌及形象的破坏。本文在充分结合相关文献资料研究及国内外优秀装配式建筑案例为支撑,结合装配式建筑构件工厂化生产的特点,总结装配式建筑的立面设计策略,从而做出既可以批量化生产构件却又不失美观的立面设计效果。

关键词： 市政道路   伸缩缝施工技术   研究  

摘要： 近年来,我国的经济有了飞快的发展,各大城市也在不断壮大,城市中的各大设施也在不断进行完善,这当中的道路建设是城市扩大规模,开展基础设施的重要有着重要的地位,对整个城市来说有着不可忽视的作用,伸缩缝施工技术的开展为城市道路的安全做了保障和有了信息的技术支撑。文章就是结合城市中实际的道路进行研究,对伸缩缝施工技术进行深入分析研究。

关键词： 群坑结构   中隔墙机械拆除   保护措施  

摘要： 群坑结构中,中隔墙将结构整体分隔成几个部分,在中隔墙附近多数会产生悬挑结构,在机械拆除中隔墙施工过程中,由于荷载堆积容易造成已完成结构悬挑端被破坏,本文通过对西虹桥商务区项目中隔墙拆除施工进行分析,归纳总结了机械拆除过程中的成品保护措施以及使用工况,以期为其他类似项目提供借鉴。

关键词： artificial antigen-presenting cells   cancer immunotherapy   intracellular hydrogelation   radical polymerization   T-cell expansion  

摘要： Robust and modular systems for T cell expansion have immense utilities for clinical development and immunoengineering research. In article 2101190, Che-Ming J. Hu and co-workers demonstrate a photoactivated intracellular radical polymerization technique that transforms live dendritic cells into a functional T-cell-stimulating biomaterial, which effectively enhances adoptive cell therapy against cancer in mice.