Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

The importance of a potential phosphorylation site in enamelin on enamel formation

Enamelin （ENAM） has three putative phosphoserines （pSers） phosphorylated by a Golgi-associated secretory pathway kinase （FAM20C） based on their distinctive Ser-x-Glu （S-x-E） motifs. Fam2OC-knockout mice show severe enamel defects similar to those in the Enam-knockout mice, implying an important role of the pSers in ENAM. To determine the role of pSer5s in ENAM, we characterized ENAMRgsc514 mice, in which Sers5 cannot be phosphorylated by FAM20C due to an E57〉Gs7 mutation in the S-x-E motif, The enamel microstructure of 4-week-old mice was examined by scanning electron microscopy. The teeth of 6-day-old mice were characterized by histology and immunohistochemistry. The protein lysates of the first lower molars of 4-day-old mice were analyzed by Western immunoblotting using antibodies against ENAM, ameloblastin and amelogenin. ENAMRgsc514 heterozygotes showed a disorganized enamel microstructure, while the homozygotes had no enamel on the dentin surface. The N-terminal fragments of ENAM in the heterozygotes were detained in the ameloblasts and localized in the mineralization front of enamel matrix, while those in the WT mice were secreted out of ameloblasts and distributed evenly in the outer 1/2 of enamel matrix. Surprisingly, the 15 kDa C-terminal fragments of ameloblastin were not detected in the molar lysates of the homozygotes. These results suggest that the phosphorylation of SerSS may be an essential posttranslational modification of ENAM and is required for the interaction with other enamel matrix molecules such as ameloblastin in mediating the structural organization of enamel matrix and protein-mineral interactions during enamel formation.

Ultrafast Coulomb explosion imaging of molecules and molecular clusters

Taking an image of their structure and a movie of their dynamics of small quantum systems have always been a dream of physicists and chemists. Laser-induced Coulomb explosion imaging(CEI) provides a great opportunity to make this dream a reality for small molecules or their aggregation — clusters. The method is unique for identifying the atomic locations with angstrom spatial resolution and capturing the structural evolution with a femtosecond time scale, in particular for imaging transient state products. This review summarizes the determination of three-dimensional equilibrium geometry of molecules and molecular cluster system through the reconstruction from the fragments momenta, and also shows that the dissociation dynamics on the complex potential energy surface can be tracked in real-time with the ultrafast CEI(UCEI).Furthermore, the detailed measurement and analysis procedures of the CEI, theoretical methods, exemplary results, and future perspectives of the technique are described.

Quantifying the Temperature Effects on the Morbidity of Digestive Diseases In an Inland Plateau-Valley City

Extreme air temperature and increased weather oscillations caused by climate change have been threatening global health.Meteorological conditions are external inducers that may trigger the onset of gastrointestinal diseases,in addition to bacterial infection or behavioral factors including smoking,alcohol consumption,and hot food consumption[1,2].

Shale Fracturability Graphic Template Based onMixed Analytic Hierar-chy Process andMutation Theory

Due to the depletion of conventional energy reserves,there has been a global shift towards non-conventional energy sources.Shale oil and gas have emerged as key alternatives.These resources have dense and heterogeneous reservoirs,which require hydraulic fracturing to extract.This process depends on identifying optimal fracturing layers,also known as‘sweet spots’.However,there is currently no uniform standard for locating these sweet spots.This paper presents a new model for evaluating fracturability that aims to address the current gap in the field.The model utilizes a hierarchical analysis approach and a mutation model,and is distinct in its use of original logging data to generate a fracturability evaluation map.Using this paper’s shale fracturing sweet spot evaluation method based on a two-step mutation model,four wells in different blocks of Fuling and Nanchuan Districts in China were validated,and the results showed that the proportion of high-yielding wells on the sweet spot line could reach 97.6%,while the proportion of low-producing wells was only 78.67%.Meanwhile,the evaluation results of the model were compared with the microseismic data,and the matching results were consistent.

索拉非尼对MHCC97-H肝癌细胞增殖、侵袭以及PRL-3蛋白表达的影响研究

目的探讨索拉非尼对体外培养MHCC97-H肝癌细胞中肝再生磷酸酶3(PRL-3)表达水平的影响,以及对肝癌细胞侵袭力的作用。方法在24、48及72 h测定经不同浓度梯度索拉非尼处理MHCC97-H肝癌细胞增殖抑制率以筛选合适的干预浓度和时间。采用MHCC97-H肝癌细胞培养传代,用索拉非尼干预处理,瑞氏吉姆萨法染色观察形态学变化,MTT法检测其增殖抑制率,Western blot法检测PRL-3蛋白表达水平,Transwell实验检测癌细胞侵袭力。结果该实验索拉非尼体外最佳干预实验浓度和时间分别为16μmol/L和48 h;索拉非尼能诱导肝癌细胞株MHCC97-H的凋亡,肝癌细胞增殖抑制率与时间和剂量呈正相关。经索拉非尼作用后PRL-3蛋白也出现不同程度下降,肝癌细胞侵袭能力明显下降。结论索拉非尼能降低MHCC97-H肝癌细胞株中PRL-3蛋白表达水平,降低肿瘤细胞侵袭力,从而诱导肝癌细胞凋亡;索拉非尼降低癌细胞的侵袭可能是通过下调PRL-3蛋白进行。

Multiphoton Ionization of Potassium Atoms in Femtosecond Laser Fields

We study the multiphoton ionization of potassium atoms in 800 nm and 400 nm femtosecond laser fields.In the 800 nm laser field,the potassium atom absorbs three photons and emits one electron via one photon resonance with the 4p intermediate state with the help of the ac-Stark shift.The resonance feature is clearly shown as an Autler-Townes(AT) splitting and is mapped out in the electron kinetic energy spectrum.In a 400 nm laser field,although one photon resonance is possible with the 5p state,no splitting is observed.The different transition amplitudes between 4s-4p and 4s-5p explain the observed results.Due to the AT effect,an unexpected peak in the photoelectron energy spectrum that violates the dipole transition rule is observed.A preliminary explanation involving the spin-orbit interaction in the p state is given to account for this component.The observed ATsplitting in the electron kinetic energy distribution can be used as an effective method to calibrate the intensity of a laser field.

我国临床试验中建立独立数据监查委员会的分析与探讨

独立数据监查委员会(IDMC)的设立对于临床研究受试者的安全性、数据的公正性有重要的意义,正成为临床试验中日益常见的部分。目前,我国临床试验中IDMC建立的合理性与规范性、实施的规范性、监管等方面尚面临挑战。本文通过查阅相关文献、法规、指导原则和国家药品监督管理局药品审评中心(CDE)药物临床试验登记与信息公示平台数据,了解其背景、职责、适用范围和各监管部门要求,分析和探讨我国临床试验中建立IDMC的现状与面临的挑战,基于相关法规要求提出建议,为我国临床试验IDMC的建立与监管提供参考。

The immunostimulatory effects of retinoblastoma cell supernatant on dendritic cells

Dendritic cells （DCs） are crucial for the induction and maintenance of tumor-specific immune responses. Studies have shown that tumor-associated DCs are immunosuppressed in some human tumors. However, phenotype and function of DCs in retinoblastoma （RB） remain unclear. RB cell supernatant （RBcs） was used to treat DCs in vitro to explore the effect of RB cells on DCs. DCs were generated from peripheral blood mono- nuclear cells of healthy donors. On day 5 of culture, DCs were treated with RBcs for 24 h, and then purified using magnetic beads. The maturation of DCs was induced by TNF-a or LPS. After treatment with RBcs, expression of co-stimulatory molecules CD80 and CD86 was elevated in DCs, accompanied by increased production of IL- 12p70, TNF-a, IL-6, IL-113, and IL-8 but decreased pro- duction of IL-10. RBcs neither inhibited DC maturation nor promoted DC apoptosis. Moreover, RBcs-exposed DCs stimulated allogenetic T cell proliferation and T cell- derived cytokine production. These results indicate that RBcs can improve DCs＇ antigen presenting function and capability to activate T cells, suggesting that RB cells may have an immunostimulatory effect on DCs, and DC- based immunotherapy may be adopted in the treatment of RB.

Microstructure Evolution and Mechanical Properties of Spray-deposited Al-21.47Si-4.73Fe-2.5Cu-0.9Mg Alloy

Al-Si-Fe-Cu-Mg alloy was prepared by spray deposition and was further processed by hot extrusion as well as T6heat-treatment.The results indicate that the microstructure of the deposited alloy is composed of primary Si particles with average size of less than 5μm,α-Al,Al_2CuMg,β-Al_5FeSi andδ-Al_4FeSi_2（rectangular shape）,and no eutectic silicon is found due to the special solidification behavior.The age hardening curves reveal two peaks.The uniform ultimate tensile strength（UTS）and the elongation of the peak-aged Al-Si-Fe-Cu-Mg alloy are 468.3 MPa,0.61% at 298 Kand 267.4MPa,6.42% at 573 K,respectively.The fracture surfaces display brittle fracture morphology at 298 K,whereas it varies to mixture of brittle and ductile failure with increasing the temperature.

模型空间上截断Toeplitz算子的范数和本质范数

借助分布函数不等式,本文得到模型空间上截断Toeplitz算子的范数和本质范数的一个上界和下界.作为应用,本文给出有界符号的截断Toeplitz紧性的一个充分必要条件.

The momentum distributions of triatomic molecular ion H_(3)^(2+) by intense laser pulses

We investigate theoretically the photoionization of triatomic molecular ion H_(3)^(2+) by numerically solving the two-dimensional time-dependent Schrödinger equations under Bohn-Oppenheimer approximation.The results show that the photoelectron momentum distributions(PMDs)of H_(3)^(2+) with different initial states are strongly dependent on the laser ellipticities and molecular orbital symmetry,and the PMDs of degenerate electronic states E^(±)are mirror images.Also,for degenerate electronic states E^(±),vortex structures appear in the PMDs by the counter-rotating circularly polarized laser pulses as the time delay between the two pulses increases,which can be explained by multicenter ionization and ultrafast photoionization model.

Long-term outcomes of intraoperative radiotherapy for early-stage breast cancer in China: amulticenter real-world study

Dear Editor,Intraoperative radiotherapy(IORT)is an accelerated par-tial breast irradiation(APBI)treatment that is accom-plished intraoperatively.Numerous clinical trials indicate that IORT is safe and effective,non-inferior to standard whole-breast external beam radiotherapy(EBRT)for low-risk patients who receive breast-conserving surgery[1-3].Nevertheless,these studies mainly included non-Asians and thus lack adequate evidence to support the value of IORT in Asian patients with breast cancer.