Investigation multi-target synergistic mechanism of Choerospondias axillaris in the treat of cerebral ischemia based on systems pharmacology and experimental verification

Background:Choerospondias axillaris(CA)is a traditional Mongolian medicine that has been proven to have a good therapeutic effect on cerebrovascular disease.Cerebral Ischemia(CI)is a severe and life-threatening cerebrovascular disease.However,the specific mechanism of action of CA in the treatment of CI is still unclear.Methods:In this study,the related targets and pathways of CA in the treatment of CI were first predicted by system pharmacology and then verified by relevant experiments.Results:The results showed that 12 active ingredients and 208 targets were selected.Further validation through protein-protein interaction(PPI)network analysis and active ingredients-target-pathway(A-T-P)network analysis has confirmed the pivotal roles of the main bioactive constituents,including quercetin,kaempferol,naringin,β-sitosterol,and gallic acid.These components exert their anti-ischemic effects by modulating key targets such as IL6,TNF,MAPK3,and CASP3,thereby regulating the PI3K-Akt,HIF-1,and MAPK signaling pathways,which are integral to processes like inflammation,apoptosis,and oxidative stress.More importantly,through experimental verification,this study confirmed our prediction that CAE significantly reduced neurological function scores,infarct volume,and the percentage of apoptosis neurons.Conclusion:This indicates that CA acts on CI through multi-target synergistic mechanism,and this study provides theoretical basis for the clinical application of CA.

Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells

OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.

Clinical Study of Magnetic Resonance Imaging,Diffusion Weighted Imaging and Dynamic Contrast-enhanced Imaging in the Diagnosis of Endometrial Carcinoma

Objective:To evaluate the value of DWI,DCE-MRI and magnetic resonance imaging(MRI)in the diagnosis of endometrial cancer.Method:The MRI,DWI and DCE-MRI imaging data of 80 patients with suspected endometrial cancer were analyzed.The diagnostic value of MRI,DWI and DCE-MRI in endometrial cancer was analyzed based on the postoperative pathological diagnosis results.The diagnostic efficacy of quantitative parameters Ktrans value,Kep value,Ve value and ADC in endometrial cancer was analyzed by ROC.Result:Among the 80 patients,61 had endometrial carcinoma and 19 had benign endometrial disease.The accuracy of MRI,DWI and DCE-MRI in the diagnosis of endometrial cancer was 57.38%,63.93%and 80.33%,respectively.The specificity was 78.95%,82.41%and 84.21%,respectively.The ADC values of endometrial cancer patients were lower than those of benign patients(P<0.05),and the values of Ktrans,Kep and Ve were higher than those of benign patients(P<0.05).The ktrans and ADC in the diagnosis of endometrial cancer were higher,which was 0.922(95%CI:0.864-0.992,P=0.000)and 0.872(95%CI:0.767-0.977.P=0.000),respectively.Conclusion:DWI and DCE-MRI had high value in the diagnosis of endometrial cancer.Its parameters,Ktrans and ADC,can be used as quantitative indicators for the early diagnosis of endometrial cancer.

Study on syndrome differentiation based on pharmacology of syndrome management system-a case of Qi and Yin deficiency syndrome

Taking the Qi and Yin deficiency syndrome as an example,the research method of pharmacology of syndrome management system was proposed.By means of text mining,systematic pharmacology and target analysis,to attempt to reveal the essence of the corresponding syndrome by studying the drugs and targets of Qi and Yin deficiency.Fourteen Chinese herbs treating Qi and Yin deficiency were retrieved and used more than 30 times,and 9,317 related targets were predicted.The common targets of action were 85.Topological analysis was carried out by using degree centrality,closeness centrality and betweenness centrality to confirm that estrogen receptor(ESR1),tumor necrosis factor(TNF),D(2)dopamine receptor(DRD2),vitamin D3 receptor(VDR),glucocorticoid receptor(NR3C1),acetylcholinesterase(ACHE)and endothelin-1(EDN1)were highly correlated with Qi and Yin deficiency syndrome.Through the target to find Qi and Yin deficiency syndrome corresponding to 17 categories of diseases.A new idea was provided for studying the biological essence of TCM clinical syndrome differentiation.

不同温度条件下鲁氏耶尔森氏菌的链特异性转录组分析

为鉴定鱼源鲁氏耶尔森氏菌(Yersinia ruckeri)SC09菌株水生环境中不同温度的转录组水平上的差异,研究采用链特异性转录组测序(Strand-specific RNA-seq)技术对菌体生理温度(28℃)和实验培养温度(37℃)下进行链特异性测序,原始数据质控后,筛选得到差异表达基因,通过KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库对差异表达基因进行富集分析,并利用Rockhopper软件筛选出的重要原核生物基因簇进行验证。结果显示,共筛选获得173个显著差异表达基因(P<0.05),其中包括58个上调基因,主要富集到一些特殊的碳水化合物代谢相关的通路中;以及115个下调基因,主要富集到双组份信号系统中与三羧酸循环相关的代谢通路上,同时部分基因富集到编码鞭毛素相关的基因簇中。结果表明,相对于37℃的实验室培养温度,在水生环境的生理温度条件下(28℃)SC09菌株拥有较高的运动性和较强的葡萄糖代谢,但相对的SC09菌株代谢一些特殊糖类的能力减弱。

池塘及稻田养殖克氏原螯虾肌肉成分与营养品质比较分析

本研究通过对池塘养殖及稻田养殖克氏原螯虾的常规营养成分、氨基酸和矿物元素等进行测定,从而科学地评定其品质特性,为稻田养殖克氏原螯虾的肌肉品质和营养价值研究提供理论依据。结果表明:稻田养殖克氏原螯虾肌肉中除脂肪含量显著低于池溏养殖克氏原螯虾(P<0.05)外,其他常规营养成分含量与池塘养殖克氏原螯虾相近;检测得到了17种氨基酸,其中包括7种必需氨基酸,呈味氨基酸含量分别为6.2975%(池塘)和6.3800%(稻田),氨基酸总含量分别为16.2300%(池塘)和16.3450%(稻田);依据氨基酸的化学评分,克氏原螯虾的第一限制性氨基酸为蛋氨酸和胱氨酸,第二限制性氨基酸为缬氨酸,必需氨基酸指数分别为78.32(池塘)和78.07(稻田);稻田养殖克氏原螯虾肌肉中钙、磷和铁含量极显著或显著(P<0.05)高于池塘养殖。池塘养殖克氏原螯虾必需氨基酸含量较高,稻田养殖克氏原螯虾具有脂肪含量低、呈味氨基酸含量丰富、矿物元素含量高等特点,池塘养殖和稻田养殖克氏原螯虾均具有氨基酸组分合理、必需氨基酸含量和种类丰富、呈味氨基酸含量高等优点。

酵母硒对鲤鱼鱼种生长性能、肌肉硒沉积量及抗病能力的影响

为研究不同水平的酵母硒对鲤鱼(Cyprinus carpio)鱼种生长性能、肌肉硒沉积量及抗病能力的影响,试验采用单因子完全随机设计,选用体重约为30 g/尾的鲤鱼鱼种,随机分为5个试验组(A1~A5,A1为空白组)和1个对照组(A6),每组3个重复,每个重复60尾。第A1~A5组分别在基础日粮中添加0、0.15、0.30、0.45、0.60 mg/kg的酵母硒,对照组在基础日粮中添加0.60 mg/kg的亚硒酸钠(Na2SeO3),试验周期为12周。分别对其生长性能指标、肌肉硒沉积量进行测定以及抗病能力进行检测。结果表明:(1)与对照组(A6)和空白组(A1)相比,鲤鱼的末重、增重率及特定生长率(SGR)均随日粮中酵母硒添加量水平的提高逐渐增大,其中以添加0.6 mg/kg酵母硒试验组的结果最高,分别为末重:(94.85±10.13)g,增重率:(217.89±36.12)%(P<0.05),SGR:(2.05±0.2)%/d。饵料系数则随日粮中酵母硒添加量水平的提高而降低,0.6 mg/kg酵母硒试验组的饵料系数最低,为(1.25±0.15);(2)0.6 mg/kg酵母硒试验组的肌肉硒沉积量为所有试验组中最大,为(0.47±0.02)mg/kg;(3)嗜水气单胞菌攻毒后空白组在第12天所有鱼均死亡,其余添加不同组分硒添加剂的试验组均有一定的保护效果,以0.6 mg/kg酵母硒试验组相对保护率最高,为46.67%。综上,在本研究中,在基础日粮中添加一定量的酵母硒可有效促进鲤鱼生长,提高饲料利用率,增加肌肉硒沉积量,提高鲤鱼的抗病能力,添加量以0.6 mg/kg为适宜。

四川彭州地区养殖虹鳟传染性造血器官坏死病病毒的分离、鉴定及病理学观察

近期,四川省成都彭州市某虹鳟养殖场暴发流行疾病,导致养殖虹鳟死亡率高达 90%。现场采样观察发现患病鱼主要症状为背部发黑,鳔壁、腹膜严重出血,心包积 液,空肠、空胃和显著肠炎。同时对病鱼进行细菌学与组织病理学检测,细菌学检查结 果为阴性,病理学观察发现脾脏有典型凝固性坏死,肝脏组织广泛变性、坏死,肠道黏 膜下层水肿,肠上皮充血及上皮细胞脱落坏死,脑膜和心外膜水肿。将病鱼的脾组织研 磨过滤除菌后,腹腔注射60尾健康虹鳟,注射组均表现为急性死亡(累计死亡率达 85%),试验鱼出现与自然发病鱼相同的症状而对照组无异常。取病鱼的脾脏组织研磨过 滤后接种胖头鲤细胞(fathead minnow cell,FHM),细胞感染3 d后出现典型的细胞病变效 应(CPE)。针对编码IHNV糖蛋白(Glycoprotein,G)基因进行逆转录-聚合酶链反应(RT- PCR)检测显示,患病鱼、人工感染病鱼和病变细胞均为IHNV阳性,扩增序列与IHNV糖 蛋白基因同源性为98.2%。对该病毒分离株的G基因进行系统发育分析,结果显示,该分 离株与亚洲分离株聚为一簇,属于JRt基因型。

新疆塘巴湖河鲈的年龄结构与生长特征

2019年5月、7月和10月在新疆额尔齐斯河附属湖泊塘巴湖(88°7’49"~88°16’38"E,47°37’2"~47°39’39"N)用刺网、地笼等渔具(网目2 cm)采集河鲈Perca fluviatilis 551尾,研究其年龄和生长特征,为塘巴湖的鱼类资源保护和开发利用提供基础数据。结果显示,样本体长55.01~307.23 mm,体质量2.45~570.06 g,年龄1~6龄,1龄为优势年龄组(占60.62%);体质量与体长的关系式为W=8×10^(-6)L^(3.1694)(R^(2)=0.9897),属匀速生长;Von Bertalanffy生长方程分别为L^(t)=475.7492[1-e^(0.1480(t-0.2307))]和W_(t)=2 262.0468[1-e^(0.1480(t-0.2307))];体长的生长速度和加速度曲线无拐点,而体质量都有拐点,拐点年龄、体长和体质量分别为7.56龄、314.95 mm和611.99 g。为加强塘巴湖的河鲈资源保护和利用,应提高捕捞规格,加大网具管理,做好禁渔和增殖放流工作,维护额尔齐斯河流域水域生态平衡。

草鱼日粮中添加饲料桑粉对其生长性能及非特异性免疫的影响

为了解在草鱼(Ctenopharyngodon idellus)日粮中添加饲料桑粉是否能够促进草鱼生长以及激活草鱼机体非特异性免疫,本试验通过在草鱼日粮中添加不同比例的饲料桑粉以及饲料桑鲜叶饲喂草鱼90 d。称取各组草鱼初始重量计算增重率、特定生长率、饲料系数。分别于饲喂后0、15、30、45、60、75、90 d尾静脉采血并收集血清检测草鱼非特异性免疫指标。试验结果显示,在草鱼日粮中添加不同比例的饲料桑粉或投喂饲料桑鲜叶均能不同程度地促进草鱼生长,但以添加量为6%的试验组效果最好,添加量为9%的试验组次之;对非特异性免疫指标检测发现,草鱼血清总超氧化物歧化酶、溶菌酶、补体C3的均呈现先升高后降低的趋势,血清杀菌活性呈现先降低后升高的趋势,以添加量为6%和9%的试验组效果较好。结果说明在草鱼日粮中添加饲料桑粉能够有效地促进草鱼生长,提高草鱼的非特异性免疫能力,可用于实际生产,且在生产中建议添加比例为9%可取得较好效果。

花䱻、唇䱻及其杂交F1代耗氧率和窒息点的比较研究

本试验利用封闭呼吸室对全长、体长规格基本一致的花䱻、唇䱻和花䱻(♀)×唇䱻(♂)杂交F1代幼鱼进行耗氧率和临界窒息点的研究。试验结果表明:水温20℃时,平均全长(11.726±0.2522)cm、体长(9.544±0.2769)cm、体质量(13.087±0.6959)g的花䱻耗氧率平均值为0.1254 mg/(g·h);平均全长(13.939±0.2420)cm、体长(11.527±0.2069)cm、体质量(21.933±0.9952)g的唇䱻耗氧率平均值为0.1099 mg/(g·h);平均全长(11.091±0.3510)cm、体长(9.046±0.3106)cm、体质量(11.182±1.0452)g的杂交F1代耗氧率平均值为0.1503 mg/(g·h)。亲本花䱻、唇䱻与杂交F1代耗氧率昼夜变化节律不一,花䱻、唇䱻白天耗氧率低于夜间,杂交F1代白天耗氧率高于夜间。花䱻、唇䱻及杂交F1代其临界窒息点随温度变化均符合2次曲线关系(R2=1),在温度为15~25℃时,其临界窒息点随温度上升而升高;同一温度下,3种鱼类窒息点相比较,花䱻>唇䱻>杂交F1代。

杂交鲟源维氏气单胞菌的分离鉴定及人工感染后组织中HSP70基因的表达分析

为了查明引起四川省某鲟鱼养殖场杂交鲟[西伯利亚鲟(Acipenser baerii)♀×施氏鲟(Acipenser schrenckii)♂]发病的病原菌并探究感染病原菌后组织中HSP70基因的表达变化,试验首先从患病濒死杂交鲟组织中进行细菌分离纯化,通过细菌生理生化特性及细菌16S rRNA基因序列分析对分离菌进行鉴定,测定半数致死量(median lethal dose,LD_(50))后进行人工回归感染试验;选择农业农村部推荐的3种水产养殖用兽药(氟苯尼考、强力霉素、磺胺甲基异口恶唑)进行药敏试验,采用实时荧光定量PCR方法测定病原菌感染后杂交鲟肝脏、肾脏、脾脏和血液HSP70基因相对表达量并进行分析。结果表明:从患病濒死杂交鲟组织中分离纯化得到1株优势菌,经细菌生理生化特性及细菌16S rRNA基因序列分析确定分离菌为维氏气单胞菌(Aeromonas veronii),分离菌对250 g杂交鲟的LD_(50)为7×10^(6) cfu/尾。感染分离菌后的杂交鲟出现与患病杂交鲟一致的临床症状,经再次分离和鉴定,得到同一株维氏气单胞菌。分离菌对氟苯尼考和磺胺甲基异口恶唑高度敏感,对强力霉素中度敏感。感染分离菌的杂交鲟肝脏、肾脏和血液HSP70基因的相对表达量在感染后第0~24小时之间呈上升趋势,在第24小时达到峰值;脾脏HSP70基因的相对表达量在感染后第0~6小时之间呈上升趋势,在第6小时达到峰值;4个组织HSP70基因的相对表达量在第24~72小时之间呈下降趋势,在第72~168小时之间保持平稳。而健康杂交鲟4个组织HSP70基因相对表达量均无明显变化。说明引起杂交鲟患病的致病性病原菌为维氏气单胞菌,HSP70基因可能参与杂交鲟感染后的应激反应。

P2X7 receptor activation aggravates NADPH oxidase 2-induced oxidative stress after intracerebral hemorrhage

Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor(P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079(100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079(100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2(ERK1/2) and nuclear factor kappa-B(NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126(2 μg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23(3.5 μg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039(100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China(approval No. TJ-A20160805) on August 26, 2016.

Superconductor-Metal Quantum Transition at the EuO/KTaO3 Interface

We report the experimental investigation of the superconductor-metal quantum phase transition of the Eu O/KTa O3 interface.Around the transition,a divergence of the dynamical critical exponent is observed,which supports the quantum Griffiths singularity in the Eu O/KTa O3 interface.The quantum Griffiths singularity could be attributed to large rare superconducting regions and quenched disorders at the interface.Our results could pave the way for studying the exotic superconducting properties at the Eu O/KTa O3 interface.

Regulatory effects of GRK2 on GPCRs and possible use as a drug target

G protein-coupled receptor kinase 2(GRK2),as a key Ser/Thr protein kinase,belong to the member of the G protein-coupled receptor kinase(GRK)family.The C-terminus of GRK2 including a plekstrin homology domain and the N-terminus of GRK2 including the RGS homology domain with binding sites for several proteins and lipids such as G protein-coupled receptors(GPCRs),G protein,phospholipase C,phosphatidylinositol 4,5-bisphosphate,extracellular signal-regulated kinase,protein kinase A and Gβγ,which can regulate the activity of GRK2.GRK2 can regulate GPCR desensitization and internalization by phosphorylating the GPCR,promoting the affinity of binding to arrestins,and uncoupling the receptors from G proteins,which play an important role in maintaining the balance between the receptors and signal transduction.Previous studies have indicated that cardiac GRK2overexpression can promote the phosphorylation ofβ-adrenergic receptor(βAR)leading toβAR desensitization and internalization,which play a pivotal role in inducing heart failure(HF)-related dysfunction and myocyte death.GRK2,as a regulator of cell function,is overexpression in hypertension.Overexpression GRK2 can inhibit Akt/e NOS signaling pathway and decreased the production and activation of e NOS leading to endothelial dysfunction.Collagen-induced arthritis induces the upregulation of GRK2 expression in fibroblast-like synoviocytes.In this review,we mainly discussed the evidence for the association between GRK2 overexpression and various diseases,which suggests that GRK2 may be an effective drug target for preventing and treating heart failure,hypertension and inflammatory disease.

Two-dimensional nanosheets as building blocks to construct three-dimensional structures for lithium storage

2D nanosheets such as graphene, silicene, phosphorene, metal dichalcogenides and MXenes are emerging and promising for lithium storage due to their ultrathin nature and corresponding chemical/physical properties. However, the serious restacking and aggregation of the 2D nanosheets are still hampering their applications. To circumvent the issues of 2D nanosheets, one efficient strategy is to construct 3D structures with hierarchical porous structures, good chemical/mechanical stabilities and tunable electrical conductivities. In this review, we firstly focus on the available synthetic approaches of 3D structures from 2D nanosheets, and then summarize the relationships between the microstructures of 3D structures built from 2D nanosheets and their electrochemical behaviors for lithium storage. On the basis of above results, some challenges are briefly discussed in the perspective of the development of various functional 3D structures.

Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats

Rheumatoid arthritis(RA)is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes(FLS).The up-regulated cellular membrane expression of G protein coupled receptor kinase 2(GRK2)of FLS plays a critical role in RA progression,the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor(EP4)signaling and FLS abnormal proliferation.Recently,although our group found that paeoniflorin-6’-O-benzene sulfonate(CP-25),a novel compound,could reverse FLS dysfunction via GRK2,little is known as to how GRK2 translocation activity is suppressed.Our findings revealed that GRK2 expression up-regulated and EP4 expression down-regulated in synovial tissues of RA patients and collagen-induced arthritis(CIA)rats,and prostaglandin E2(PGE2)level increased in arthritis.CP-25 could down-regulate GRK2 expression,up-regulate EP4 expression,and improve synovitis of CIA rats.CP-25 and GRK2 inhibitors(paroxetine or GSK180736 A)inhibited the abnormal proliferation of FLS in RA patients and CIA rats by down-regulating GRK2 translocation to EP4 receptor.The results of microscale thermophoresis(MST),cellular thermal shift assay,and inhibition of kinase activity assay indicated that CP-25 could directly target GRK2,increase the protein stability of GRK2 in cells,and inhibit GRK2 kinase activity.The docking of CP-25 and GRK2 suggested that the kinase domain of GRK2 might be an important active pocket for CP-25.G201,K220,K230,A321,and D335 in kinase domain of GRK2 might form hydrogen bonds with CP-25.Site-directed mutagenesis and co-immunoprecipitation assay further revealed that CP-25 down-regulated the interaction of GRK2 and EP4 via controlling the key amino acid residue of Ala321 of GRK2.Our data demonstrate that FLS proliferation is regulated by GRK2 translocation to EP4.Targeted inhibition of GRK2 kinase domain by CP-25 improves FLS function and represents an innovative drug for the treatment of RA by targeting GRK2.

Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis

Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems.The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive.Here,a single-cell study involving 40043 cells is conducted,and a total of 10 distinct cell clusters are identified from five different groups.A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties.The increased immature neutrophils,Ly6C+CCR2hi monocytes,and S100a8hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant.The enrichment of mature neutrophils,FcgR1hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response.Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration.Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis.These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of‘osteoimmune-smart’biomaterials in the bone regeneration field.

Cellphone application rehabilitation management and evaluations of cardiopulmonary function and motor development in infants with congenital heart disease:a pilot study

Congenital heart disease(CHD)has an estimated prevalence of 0.9%,with 0.3%requiring interventional or surgical intervention very early in life.Currently,CHD surgery tends to be performed at a younger age.The continued management of the condition is dependent on postoperative care and rehabilitation since the success rate of surgery has significantly increased[1,2].According to American Heart Association guidelines published in 2012.

Bioinformatic identification of key genes and pathways that may be involved in the pathogenesis of HBV-associated acute liver failure

In order to explore the molecular mechanisms behind the pathogenesis of acute liver failure(ALF)associated with hepatitis B virus(HBV)infection,the present study aimed to identify potential key genes and pathways involved using samples from patients with HBV-associated ALF.The GSE38941 array dataset was downloaded from the Gene Expression Omnibus database,and differentially expressed genes(DEGs)between 10 liver samples from 10 healthy donors and 17 liver specimens from 4 patients with HBV-associated ALF were analyzed using the Linear Models for Microarray Data package.Gene Ontology and KEGG pathway enrichment analyses of the DEGs were performed,followed by functional annotation of the genes and construction of a proteineprotein interaction(PPI)network.Subnetwork modules were subsequently identified and analyzed.In total,3142 DEGs were identified,of which 1755 were upregulated and 1387 were downregulated.The extracellular exosome,immune response,and inflammatory response pathways may potentially be used as biomarkers of ALF pathogenesis.In total,17 genes(including CCR5,CXCR4,ALB,C3,VGEFA,and IGF1)were identified as hub genes in the PPI network and may therefore be potential marker genes for HBV-associated ALF.