Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

An Optimized System of Random Forest Model by Global Harmony Search with Generalized Opposition-Based Learning for Forecasting TBM Advance Rate

As massive underground projects have become popular in dense urban cities,a problem has arisen:which model predicts the best for Tunnel Boring Machine(TBM)performance in these tunneling projects?However,performance level of TBMs in complex geological conditions is still a great challenge for practitioners and researchers.On the other hand,a reliable and accurate prediction of TBM performance is essential to planning an applicable tunnel construction schedule.The performance of TBM is very difficult to estimate due to various geotechnical and geological factors and machine specifications.The previously-proposed intelligent techniques in this field are mostly based on a single or base model with a low level of accuracy.Hence,this study aims to introduce a hybrid randomforest(RF)technique optimized by global harmony search with generalized oppositionbased learning(GOGHS)for forecasting TBM advance rate(AR).Optimizing the RF hyper-parameters in terms of,e.g.,tree number and maximum tree depth is the main objective of using the GOGHS-RF model.In the modelling of this study,a comprehensive databasewith themost influential parameters onTBMtogetherwithTBM AR were used as input and output variables,respectively.To examine the capability and power of the GOGHSRF model,three more hybrid models of particle swarm optimization-RF,genetic algorithm-RF and artificial bee colony-RF were also constructed to forecast TBM AR.Evaluation of the developed models was performed by calculating several performance indices,including determination coefficient(R2),root-mean-square-error(RMSE),and mean-absolute-percentage-error(MAPE).The results showed that theGOGHS-RF is a more accurate technique for estimatingTBMAR compared to the other applied models.The newly-developedGOGHS-RFmodel enjoyed R2=0.9937 and 0.9844,respectively,for train and test stages,which are higher than a pre-developed RF.Also,the importance of the input parameters was interpreted through the SHapley Additive exPlanations(SHAP)method,and it was found that thrust force per cutter is the most important variable on TBMAR.The GOGHS-RF model can be used in mechanized tunnel projects for predicting and checking performance.

Impact of different interaction behavior on epidemic spreading in time-dependent social networks

We investigate the impact of pairwise and group interactions on the spread of epidemics through an activity-driven model based on time-dependent networks.The effects of pairwise/group interaction proportion and pairwise/group interaction intensity are explored by extensive simulation and theoretical analysis.It is demonstrated that altering the group interaction proportion can either hinder or enhance the spread of epidemics,depending on the relative social intensity of group and pairwise interactions.As the group interaction proportion decreases,the impact of reducing group social intensity diminishes.The ratio of group and pairwise social intensity can affect the effect of group interaction proportion on the scale of infection.A weak heterogeneous activity distribution can raise the epidemic threshold,and reduce the scale of infection.These results benefit the design of epidemic control strategy.

Materials,preparation,performances and mechanism of polyurethane modified asphalt and its mixture:A systematic review

With the rapid development of asphalt pavement technology,it has attracted considerable attention to improving the durability of asphalt pavement.An effective action is to use modified asphalt with high performance and durability.Polyurethane(PU)has been used in asphalt pavement engineering to enhance the durability and service life of asphalt pavement because of its excellent high-temperature performance,toughness,wear resistance,aging resistance and oil resistance.However,PU modified asphalt technology is still in the exploratory stage.The preparation,modification mechanism and working performances of PU modified asphalt need to be further clarified.Therefore,this paper summarized the research progress of PU modified asphalt and its mixture.The composition of PU modified asphalt was introduced.The addition methods of PU materials and preparation process parameters of the PU modified asphalt were determined.The modification mechanism of PU on asphalt was discussed.The effects of polyurethane on asphalt were analyzed and the road performances of its mixture were evaluated.Finally,the development tendency towards PU modified asphalt and its mixture were forecasted.

Magnetic ordering induced magnetodielectric effect in Ho_(2)Cu_(2)O_(5) and Yb_(2)Cu_(2)O_(5)

Materials with strongly coupled magnetic and electronic degrees of freedom provide new possibilities for practical applications.In this paper,we have investigated the structure,magnetic property,and magnetodielectric(MD) effect in Ho_(2)Cu_(2)O_(5) and Yb_(2)Cu_(2)O_(5) poly crystalline samples,which possess a non-centrosymmetric polar structure with space group Pna2_(1).In Ho_(2)Cu_(2)O_(5),Ho^(3+) and Cu^(2+) sublattices order simultaneously,exhibiting a typical paramagnetic to antiferromagnetic transition at 13.1 K.While for Yb_(2)Cu_(2)O_(5),two magnetic transitions which originate from the orderings of Yb^(3+)(7.8 K) and Cu^(2+)(13.5 K) sublattices are observed.A magnetic field induced metamagnetic transition is obtained in these two cuprates below Neel temperature(T_(N)).By means of dielectric measurement,distinct MD effect is demonstrated by the dielectric anomaly at T_(N.)Meanwhile,the MD effect is found to be directly related to the metamagnetic transition.Due to the specific spin configuration and different spin evolution in the magnetic field,a positive MD effect is formed in Ho_(2)Cu_(2)O_(5),and a negative one is observed in Yb_(2)Cu_(2)O_(5).The spontaneous dielectric anomaly at T_(N) is regarded as arising from the shifts in optical phonon frequencies,and the magnetoelectric coupling is used to interpret the magnetic field induced MD effect.Moreover,an H-T phase diagram is constructed for Ho_(2)Cu_(2)O_(5) and Yb_(2)Cu_(2)O_(5) based on the results of isothermal magnetic and dielectric hysteresis loops.

新型硅胶管逆行置管治疗少儿泪小管断裂的疗效分析

目的:观察新型硅胶(RS-1型)泪道引流管逆行置管治疗少儿泪小管断裂的临床效果。方法:回顾性分析于2016-03/2019-11邯郸市眼科医院及邯郸市中心医院收治的37例37眼泪小管断裂患者的临床资料。所有患者术中逆行植入新型硅胶管,8-0可吸收缝线吻合泪小管断端,6-0可吸收缝线间断吻合“内眦韧带-眼轮匝”复合体,间断缝合肌肉、皮下组织、皮肤伤口及结膜面伤口。术后2~3mo拔管,随访6~12mo,观察泪道通畅情况及溢泪症状。结果:泪小管断裂37眼中,临床治愈31眼(84%),好转5眼(14%),无效1眼(3%),总有效率达97%。所有患者均未发生泪小点撕裂、泪小点位置异常、成角畸形等相关并发症,无效1眼(3%)为合并骨性泪小管骨折,无明显溢泪症状。结论:新型硅胶管逆行置管具有操作简便、术后刺激轻、置管状态安全、吻合效果显著等特点,逆行置管能较好保护泪小点。

Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro

AIM:To investigate the role of insulin-like growth factor binding protein-7 (IGFBP-7) in the activation and transdifferentiation of hepatic stellate cells (HSC) in vitro.METHODS:Rat HSC-T6 cells were cultured in separate dishes and treated with various concentration of transforming growth factor (TGF)-β1,IGFBP-7 or antiIGFBP-7 antibody for 24 h.The supernatant or a cytoplasm suspension was obtained from cultured HSC,followed by transfer of cells to form cell-coated dishes.Immunocytochemistry and Western blotting were used to analyze the expression of IGFBP-7 induced by TGF-β1 and the level of fibronectin,collagen and α-smooth muscle actin (SMA).The pro-apoptotic effect of antiIGFBP-7 antibody was determined by flow cytometry.RESULTS:Immunocytochemistry and Western blotting revealed that the expression of IGFBP-7 in TGF-β1 treated HSC was significantly up-regulated compared to that in the control group.In addition,fibronectin,collagen and α-SMA also showed enhanced expression in accordance with the transdifferentiation process in a dose-dependent manner to some extent.Moreover,flow cytometry suggested that anti-IGFBP-7 antibody induced apoptosis of activated HSC,which is responsible for the development of liver fibrosis,and may represent a novel pathway and target for therapeutic intervention.CONCLUSION:IGFBP-7 showed increased expression in activated HSC and played an important role in the activation and transdifferentiation process of HSC.AntiIGFBP-7 antibody may ameliorate liver fibrogenesis.

Research Progress of Refractory High Entropy Alloys:A Review

Owing to superior comprehensive performance than conventional superalloys at high temperature,refractory high entropy alloy(RHEA)is becoming a promising candidate for the next generation high-temperature material.Herein,contemporary aspects of corresponding development of RHEAs are reviewed to discuss various factors affecting the organization structure and service performance.It mainly covers alloying system and strengthening mechanism,the preparation method,plastic deformation and the related mechanism,as well as microstructure control by heat treatment.Firstly,the alloy systems and strengthening mechanism are introduced.This is followed by different preparation methods and the comparison of strengths and shortcomings based on different RHEAs.Then,hot deformation behavior and plastic deformation under different loadings are analyzed.Based on this,the influence of heat treatment on microstructures prior to and after the deformation is further summarized.Finally,some important research areas to be carried out in future are pointed out.This review will give a deep understanding of the effects of different factors on the service performance and provide scientific guide in designing RHEAs with improved performance.

Total closure of pancreatic section for end-to-side pancreaticojejunostomy decreases incidence of pancreatic fistula in pancreaticoduodenectomy

BACKGROUND： Postoperative pancreatic fistula （POPF） is a serious complication and results in prolonged hospitalization and high mortality. The present study aimed to evaluate the safety and effectiveness of total closure of pancreatic section for end-to-side pancreaticojejunostomy in pancreaticoduodenectomy （PD）. METHODS： This was a prospective randomized clinical trial comparing the outcomes of PD between patients who un- derwent total closure of pancreatic section for end-to-side pancreaticojejunostomy （Group A） vs those who underwent conventional pancreaticojejunostomy （Group B）. The primary endpoint was the incidence of pancreatic fistula. Secondary endpoints were morbidity and mortality rates. RESULTS： One hundred twenty-three patients were included in this study. The POPF rate was significantly lower in Group A than that in Group B （4.8% vs 16.7%, P〈0.05）. About 38.3% patients in Group B developed one or more complications; this rate was 14.3% in Group A （P〈0.01）. The wound/abdomi- nal infection rate was also much higher in Group B than that in Group A （20.0% vs 6.3%, P〈0.05）. Furthermore, the average hospital stays of the two groups were 18 days in Group A, and 24 days in Group B, respectively （P〈0.001）. However, there was no difference in the probability of mortality, biliary leakage,delayed gastric emptying, and pulmonary infection between the two groups. CONCLUSION： Total closure of pancreatic section for end-to- side pancreaticojejunostomy is a safe and effective method for pancreaticojejunostomy in PD.

Fabrication of extreme wettability surface for controllable droplet manipulation over a wide temperature range

Droplet controllable manipulation over a wide temperature range has promising applications in microelectronic heat dissipation, inkjet printing, and high temperature microfluidic system. However, the fabrication of a platform for controllable droplet manipulation using the methods commonly used in industry remains a tremendously challenge. The popular method of controlling droplets is highly dependent on external energy input and has relatively poor controllability in terms of droplet motion behaviors and manipulation environment, such as distance, velocity, direction and a wide temperature range. Here, we report a facile and industrially applicable method for preparing Al superhydrophobic (S-phobic) surfaces, which enables controlled droplet bouncing, evaporation, and transport over a wide temperature range. Systematic mechanistic studies are also investigated. Extreme wettability surfaces were prepared on Al substrate by a composite process of electrochemical mask etching and micro-milling. To investigate the evaporation process and thermal coupling characteristics, controlled evaporation and controlled bouncing of droplet in a wide temperature range were conducted. Based on the evaporation regulation and bouncing mechanism of droplets on an extreme wettability surface, by using Laplace pressure gradients and temperature gradients, we realized controlled transport of droplets with confluence, split-flow, and gravity-resistant transport over a wide temperature range, offering a potential platform for a series of applications, such as new drug candidates and water collection.

中深层同轴套管式地埋管换热器取热特性

中深层地热资源丰富,具有清洁环保、稳定可靠等特点,利用中深层地热向地面建筑物供热越来越受到人们重视.文中在考虑岩土层分层的前提下,建立中深层套管式地埋管换热器传热模型,基于有限差分法将其离散求解,并将求解的结果与某实际项目的实测数据进行比对,在此基础上对中深层套管式地埋管换热器的传热特性做了进一步模拟研究.研究结果表明:特定工况下,在系统连续运行整个采暖季后对钻井周围岩土层温度场的影响半径为7.7 m;系统取热量随着套管式换热器外径的增大而增加;当工质循环流量由35 m^(3)/h增加到42 m^(3)/h,管道底部温度仅变化2.2%;延米换热功率不宜大于150 W;当回填材料导热系数由2 W/(m·K)增加到2.5 W/(m·K)时,管底温度上升比例仅为1.9%,即回填材料导热系数达到一定值时再增大导热系数对进出水温度影响不大.

A 3-kHz Er:YAG single-frequency laser with a‘triple-reflection’configuration on a piezoelectric actuator

A novel Er:YAG laser system operating at 1645 nm with high pulse-repetition-frequency(PRF)of kHz level is demonstrated.A ring cavity with double gain medium end-pumped by two fiber lasers is utilized to obtain high pulse energy.A novel‘triple-reflection’configuration on a piezoelectric actuator(PZT)is adopted to achieve high-repetition-rate at 3-kHz operation with the ramp-fire locking method.Single frequency pulses with maximum average power of 18.3 W at 3 kHz are obtained,and the pulse duration time is 318 ns.The full line width at half maximum(FWHM)of the pulses measured by the heterodyne technique is 1.71 MHz at 3 kHz.To the best of our knowledge,this is the highest PRF single-frequency laser pulses achieved based Er:YAG gain medium.

球周注射尼莫地平对兔慢性高眼压致视网膜神经节细胞凋亡的干预作用

目的观察眼球周注射尼莫地平对慢性高眼压兔网膜视神经节细胞凋亡的干预作用。方法选用健康新西兰白兔30只,随机分为A、B、C、D、E 5组,每组6只。A组为正常组,其余各组均行复方卡波姆复制慢性高眼压模型,B组注射生理盐水,C、D、E组分别球周注射低(0.125 mg)、中(0.250 mg)、高(0.500 mg)剂量尼莫地平(NMD)注射液。第2周处死动物取视网膜组织行免疫组化、TUNEL法检测及HE形态学观察,比较各组间的差异。结果 B淋巴细胞瘤2基因(Bcl-2)在B、C组呈低表达,在D、E两组呈高表达,D、E两组均高于B、C两组,差异有统计学意义(P<0.05)。B淋巴细胞瘤2基因相关蛋白X(Bax)在B、C组呈高表达,随NMD剂量增高阳性细胞表达量降低,D、E组呈低表达,差异有统计学意义(P<0.05)。TUNEL检测,在B、C组呈高表达,在D、E组呈低表达,差异有统计学意义(P<0.05)。结论尼莫地平注射液球周注射对兔慢性高眼压视网膜神经节细胞凋亡有积极的保护作用。

Extensive calcifications in portal venous system in a patient with hepatocarcinoma

Calcification of the portal venous system is a rare entity that can be incidentally discovered during computed tomography(CT).We describe a case of extensive calcifications in the portal venous system in a middleaged male patient with hepatocellular carcinoma(HCC).This patient presented with epigastric pain that had no obvious origin prior to admission.Laboratory examinations were positive for hepatitis B surface antigen andα-fetoprotein,and severe esophageal and gastric varices were detected during gastroscopy.Abdominal X-ray plain film showed well-defined linear and tracklike calcification,with irregular margins directed along the course of the portal venous system.CT revealed extensive calcifications along the course of the portal,splenic,superior mesenteric and gastroesophageal veins.He underwent splenectomy 22 years ago due to splenomegaly and partial hepatectomy seven months before because of HCC of low-grade differentiation,confirmed by pathology.Finally,the patient was diagnosed with postoperative recurrent HCC and extensive portal venous system calcification after selective hepatic angiography under digital subtraction angiography.

Role of oxysterol-binding protein-related proteins in malignant human tumours

The oxysterol-binding protein-related protein(ORP)family is a group of proteins that mediate oxysterol metabolism and bioactivity in cells.ORPs constitute a large family of lipid transfer proteins.Much of the current evidence indicates that certain members of the family of oxysterol-binding proteins(OSBPs)can lead to cancer.Many studies have revealed the putative roles of OSBPs in various cancer types.However,the exact effects and mechanisms of action of members of the OSBP/ORP family in cancer initiation and progression are currently unclear.This review focuses on ORP family members that can accelerate human tumour cell proliferation,migration,and invasion.The mechanisms and functions of various ORPs are introduced in detail.We also attempt to identify the roles of these proteins in malignant tumours with the ultimate aim of determining the exact role of the OSBP/ORP family in human tumour cells.

JS-K对人结肠癌细胞HCT116增殖及凋亡的影响

目的研究JS-K对人结肠癌细胞HCT116增殖及凋亡的影响。方法不同浓度JS-K处理HCT116细胞48 h后,采用MTS法检测JS-K对HCT116细胞增殖活性的影响;PI单染流式细胞术检测JS-K对HCT116细胞周期的影响;Annexin V-FITC/PI双染流式细胞术检测JS-K对HCT116细胞凋亡的影响;Texas Red-X鬼笔环肽荧光染色观察细胞骨架形态;实时荧光定量聚合酶链反应检测Bcl-2家族基因mRNA表达。结果JS-K对人结肠癌细胞HCT116增殖有抑制作用,且呈浓度和时间依赖性(P<0.05)。JS-K诱导HCT116细胞被阻滞在G2/M期(P<0.05)。JS-K可致HCT116细胞发生晚期凋亡(P<0.05)。JS-K可改变HCT116细胞骨架形态、微丝结构与分布。随着JS-K浓度增加,促凋亡基因Bax、Bik、Bim、Puma mRNA相对表达量上调,抗凋亡基因Mcl-1 mRNA相对表达量下调(P<0.05)。结论JS-K对人结肠癌HCT116细胞增殖有明显抑制作用,通过调节Bcl-2家族基因表达,阻滞细胞G2/M期,促进细胞发生晚期凋亡。

Influence of Beta-Cyclodextrin Functionalized Tin Phenylphosphonate on the Thermal Stability and Flame Retardancy of Epoxy Composites

To enhance the thermal stability and flame retardancy of epoxy resin(EP),beta-cyclodextrin(β-CD)is successfully introduced into the layered tin phenylphosphonate(SnPP),which is incorporated into EP matrix for preparing EP/β-CD@SnPP composites.The results indicate that the addition ofβ-CD@SnPP obviously improve the thermal stability and residual yield of EP composites at higher temperature.When the amount ofβ-CD@SnPP is only 4 wt%,EP/4β-CD@SnPP composites pass V-1 rating,and LOI value is up to 30.8%.Meanwhile,β-CD@SnPP effectively suppress the heat release and reduce the smoke production of EP/β-CD@SnPP composites in combustion,and the peak heat release rate(PHRR),total heat release(THR),smoke production rate(SPR)of EP/6β-CD@SnPP composites reduce by 28.4%,33.0%and 44.8%by comparison with those of pure EP.The good flame retardancy and smoke suppression are ascribed to the synergistic effect of excellent carbon-forming capability and fire retardancy ofβ-CD@SnPP.

Microstructure and properties of AlSi7Mg alloy fabricated by selective laser melting

The AlSi7Mg alloy was fabricated by selective laser melting(SLM),and its microstructure and properties at different building directions after heat treatment were analyzed.Results show that the microstructure of SLM AlSi7Mg samples containes three zones:fine grain zone,coarse grain zone,and heat affected zone.The fine-grain regions locate inside the molten pool,and the grains are equiaxed.The coarse-grain regions locate in the overlap of molten pools.After T6 treatment,the microstructure at the molten pool boundary is still the network eutectic Si,but the network structure becomes discrete,and is composed of intermittent,chain-like eutectic Si particles.The yield strength at three directions(xy,45°,z direction)of the AlSi7Mg alloy samples fabricated by SLM is improved after T6 heat treatment.The fracture mechanism of the samples is a mixed ductile and brittle fracture before heat treatment and ductile fracture after heat treatment.

Effect of B-Site Ordering on the Magnetic Order in Multifunctional La2NiMnO6 Double Perovskite

To obtain various Ni/Mn orderings,we use a low-temperature synthesized method to modulate the Ni/Mn ordering of the ferromagnetic-ferroelastic La2NiMnO6 compound,and the Ni/Mn ordering is estimated by the low-temperature saturation magnetism.The microstructures,crystal structures and magnetic properties are investigated,and the Landau theory are used to describe the form and magnitude of the coupling effects between Ni/Mn ordering and magnetic order parameters.It is predicted that the Ni/Mn ordering would be a strong coupling effect with the Curie transition temperatures if the La2NiMnO6 sample stoichiometry is close.