Long non-coding RNA-AK138945 regulates myocardial ischemia-reperfusion injury via the miR-1-GRP94 signaling pathway

Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.

比色法测碘酸铜溶度积常数实验的改进

现行教材中以氨水做显色剂,比色法测定碘酸铜溶度积常数,有一定的环境污染。本实验以甘氨酸替代氨水作为显色剂,通过紫外-可见吸收光谱考察甘氨酸与铜离子反应的时间以及甘氨酸的最佳用量,从而获得配制甘氨酸合铜(Ⅱ)溶液的最佳条件,进而测定该条件下配制的各溶液的吸光度,最终获得碘酸铜饱和溶液中铜离子的浓度并计算得到与文献值接近的溶度积常数。该实验可避免实验过程中挥发性腐蚀性气体的释放,且溶液可浓缩回收甘氨酸合铜(Ⅱ),避免了环境污染,是一种绿色实验方法,在人数众多的基础实验教学中具有适用性。

Enhancing the compatibility of the amyloid-dye hybrid nanostructure for improved photo-biocatalysis

Artificial photosynthesis is significant for renewable energy generation,sustainable development,and environmental protection.Dye-protein hybrids are promising for developing photosynthesis mimics(e.g.,photo-biocatalysis),but their performances are far lower than the plant photosystems,partially because of the incompatibility between dye and the protein matrix that limits excited state electron transfer of the included dyes.Here,using ThT-insulin amyloid assembly as a model system,we proposed that increasing the dye-protein compatibility could lead to the improved photo-biocatalytic performance.A ThT derivative,ThTPD,was designed with the same electron acceptor but extended π-conjugated donor structure.When integrated into the insulin amyloid,the extended π-conjugated donor structure allowed increased binding affinity and energy with the amyloid matrix,thus better electron transport to the mediator to drive the photocatalytic reaction.Meanwhile,compared with ThT, ThTPD exhibited improved light absorption and longer excited state lifetime.The photo-biocatalytic performance of ThTPD-insulin amyloid was greatly improved as compared with that of ThT in reduced nicotinamide adenine dinucleotide(NADH) regeneration.When integrating with NADH-dependent L-glutamate reductase,the efficiency of the ThTPD-insulin amyloid hybrid was 2.8-fold higher than that of ThT in glutamate generation,showing promising feature in biocatalytic solar-to-chemical conversion.

Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 signaling pathway,the activation of which has been demonstrated to promote M1 polarization in macrophages.Conclusions:GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.

Anisotropic TV Regularization in Electrical Impedance Tomography: An Experimental Study

Total variation (TV) regularization method is a typical method to preserve the discontinuities structure in EIT. Isotropic TV and anisotropic TV are two well-known variants of TV. The main differences between them are that the latter tends to distort the reconstructed internal inhomogeneities along the coordinate axis. In this article, we adopt the alternating direction method of multipliers (ADMM) to overcome the non-differentiability of the anisotropic TV and verify the characteristics of anisotropic TV regularization by the tank experiments.

Weak Graph Map Homotopy and Its Applications

The authors introduce a notion of a weak graph map homotopy(they call it M-homotopy),discuss its properties and applications.They prove that the weak graph map homotopy equivalence between graphs coincides with the graph homotopy equivalence defined by Yau et al in 2001.The difference between them is that the weak graph map homotopy transformation is defined in terms of maps,while the graph homotopy transformation is defined by means of combinatorial operations.They discuss its advantages over the graph homotopy transformation.As its applications,they investigate the mapping class group of a graph and the 1-order M P-homotopy group of a pointed simple graph.Moreover,they show that the 1-order M P-homotopy group of a pointed simple graph is invariant up to the weak graph map homotopy equivalence.

国内中西医结合病房的药物治疗相关问题研究

对中西医结合病房住院患者开展药物治疗相关问题的研究具有挑战性,我们希望明确此类患者的药物治疗相关问题发生情况及其影响因素。回顾性分析我院中西医结合病房相关资料,以欧洲药学监护联盟分类工具V9.0,对药物治疗问题进行确证和分类,并开展相关性分析。研究共纳入1606名患者,其中至少出现1种药物治疗相关问题的人数约占一半(47.6%)。问题主要来源于PPI(21.7%),内源性补充剂(15.4%)和中药制剂(8.7%)等。最常见的原因类别包括“给药途径错误”(18.4%)、“不适当联合用药”(16.7%)、“疗程过长”(13.0%)和“选择了不适当的用药剂型”(12.1%)。约63.6%的干预措施被接受和实施。出现问题最可能的相关因素是“过度联用药物”和“住院时间≥10天”。中西医结合病房药物治疗相关问题的存在较为普遍,在我们提供的策略基础上有必要开展进一步研究。

抗两性蛋白抗体相关副肿瘤性脑干脑炎伴食管神经内分泌癌1例

副肿瘤神经综合征(PNS)是恶性肿瘤继发的自身免疫反应所致的一组异质性疾病, 可累及神经系统的任何部分。抗两性蛋白抗体为PNS高风险抗体之一, 常伴发小细胞肺癌及乳腺癌, 而肺外神经内分泌癌少见。我们报道1例伴发食管神经内分泌癌的抗两性蛋白抗体相关副肿瘤性脑干脑炎患者。通过氟脱氧葡萄糖正电子发射体层摄影发现肿瘤, 由胃镜活组织检查病理证实。患者经人免疫球蛋白和糖皮质激素治疗后, 神经系统症状部分改善。最终预后与伴发肿瘤密切相关。

Commuting Involutions with Fixed Point Set of Constant Codimension

Special generators of the unoriented cobordism ring MO* are constructed to determine the groups Jn,kτ of n-dimensional cobordism classes in MOn containing a representative Mn admitting a （Z2）k -action with fixed point set of constant codimension.

Comparison of benzothiazole-based dyes for sensitive DNA detection

For efficient and quantitative DNA detection,fluorescence staining is the most often explored approach,which relies on non-covalent binding of dyes with double stranded DNA(dsDNA).Ethidium bromide(EB)is the most classic DNA stain,but suffers from its high carcinogenicity.A series of less toxic alternatives were developed,many of which contain the core structure of the benzothiazole ring.However,the relationship between the structure and the DNA detection performance was not illustrated.Herein,five benzothiazole dyes,namely thiazole orange,SYBR Green I,Pico Green,SYBR Safe,and thioflavine-T,were compared for DNA detection through direct fluorescence and gel electrophoresis,with particular focus on the structure-performance relationship.It turned out that SYBR Green I is currently the best choice for DNA detection.The results in this work may be useful for future DNA-staining dye developments.

Hot deformation behavior and microstructure evolution of the laser solid formed TC4 titanium alloy

Hot compressive experiments of the laser solid formed(LSFed)TC4 titanium alloy were conducted at a wide temperature range of 650-950℃and strain rate of 0.01-10 s^(-1).The Arrheniustype constitutive models of the LSFed TC4 alloy were established at the temperature range of 800-950℃and of 650-800℃,respectively.The average relative error between the predicted stresses and experimental values in those two temperature ranges are 10.4%and 8.3%,respectively,indicating that the prediction models constructed in this paper are in a good agreement with experimental data.Processing maps were established by the principle of dynamic materials modeling on the basis of the data achieved from the hot compression experiments.The processing parameters corresponding to the stable and unstable regions of material deformation can be determined from the processing maps.The microstructure evolution of the stable and unstable regions of the samples after tests were observed.Finally,the effect of hot compressive parameters on the microstructure were investigated to research the dynamic recrystallization and the texture of the deformed LSFed TC4 alloy.

The Gold Coast criteria increases the diagnostic sensitivity for amyotrophic lateral sclerosis in a Chinese population

Objectives:The aim of this study was to assess and compare the diagnostic utility of a new diagnostic criteria for amyotrophic lateral sclerosis(ALS),abbreviated as the‘Gold Coast Criteria’,with the revised El Escorial(rEEC)and Awaji criteria.Methods:Clinical and electrophysiological data of 1185 patients from January 2014 to December 2019 in the Peking Union Medical College Hospital ALS database were reviewed.The sensitivity of the Gold Coast criteria was compared to that of the possible rEEC and Awaji criteria(defined by the proportion of patients categorized as definite,probable,or possible ALS).Results:A final diagnosis of ALS was recorded in 1162 patients.The sensitivity of the Gold Coast criteria(96.6%,95%confidence interval[CI]=95.3%-97.5%)was greater than that of the rEEC(85.1%,95%CI=82.9%-87.1%)and Awaji(85.3%,95%CI=83.2%-87.3%).In addition,the sensitivity of the novel criteria maintained robust across subgroups,and the advantage was more prominent in limb-onset ALS patients and those who completed electromyographic tests.In those who did not achieve any of the rEEC diagnostic categories,the sensitivity of Gold Coast criteria was 84.4%.Conclusions:The current study demonstrated that the Gold Coast criteria exhibited greater diagnostic sensitivity than the rEEC and Awaji criteria in a Chinese ALS population.The application of the Gold Coast criteria should be considered in clinical practice and future therapeutic trials.

Orientable Small Covers over a Product Space

A small cover is a closed manifold M^n with a locally standard(Z_2)~n-action such that its orbit space is a simple convex polytope P^n. Let Δ~n denote an n-simplex and P(m) an m-gon. This paper gives formulas for calculating the number of D-J equivalent classes and equivariant homeomorphism classes of orientable small covers over the product space Δ^(n_1)×Δ^(n_2)× P(m), where n_1 is odd.

Two Commuting Involutions Fixing RP_(1)(2m+1)∪RP_(2)(2m+1)

Let Z2 denote a cyclic group of 2 order and Z_(2)^(2)=Z_(2)×Z_(2)the direct product of groups.Suppose that(M,Φ)is a closed and smooth manifold M with a smooth Z_(2)^(2)-action whose fixed point set is the disjoint union of two real projective spaces with the same dimension.In this paper,the authors give a sufficient condition on the fixed data of the action for(M,Φ)bounding equivariantly.

Double-Stranded DNA Matrix for Photosensitization Switching

Photosensitization,originated from the activation of triplet states,is the basis of many photodynamic applications,but often competes with a series of nonradiative processes.Herein,we communicate a new function of double-stranded DNA(dsDNA)for label-free photosensitization switching.Up to∼70-fold singlet oxygen generation boosting was observed for SYBR Green I(SG)upon binding with dsDNA.Detailed photophysical and theoretical studies have revealed the role of dsDNA as a matrix,which could efficiently suppress the nonradiative transitions of SG.