Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

MiR-142-3p Regulates ILC1s by Targeting HMGB1 via the NF-κB Pathway in a Mouse Model of Early Pregnancy Loss

Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.

Dual-doping for enhancing chemical stability of functional anionic units in sulfide for high-performance all-solid-state lithium batteries

The sulfide-based solid-state electrolytes(SEs)reactivity toward moisture and Li-metal are huge barriers that impede their large-scale manufactu ring and applications in all-solid-state lithium batteries(ASSLBs).Herein,we proposed an Al and O dual-doped strategy for Li_(3)PS_(4)SE to regulate the chemical/electrochemical stability of anionic PS_(4)^(3-)tetrahedra to mitigate structural hydrolysis and parasitic reactions at the SE/Li interface.The optimized Li_(3.08)A_(10.04)P_(0.96)S_(3.92)O_(0.08)SE presents the highestσLi+of 3.27 mS cm^(-1),which is~6.8 times higher than the pristine Li_(3)PS_(4)and excellently inhibits the structural hydrolysis for~25 min@25%humidity at RT.DFT calculations confirmed that the enhanced chemical stability was revealed to the intrinsically stable entities,e.g.,POS33-units.Moreover,Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)SE cycled stably in Li//Li symmetric cell over 1000 h@0.1 mA cm^(-2)/0.1 mA h cm^(-2),could be revealed to Li-Al alloy and Li_(2)Oat SE/Li interface impeding the growth of Li-dendrites during cycling.Resultantly,LNO@LCO/Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)/Li-In cell delivered initial discharge capacities of 129.8 mA h g^(-1)and 83.74%capacity retention over 300 cycles@0.2 C at RT.Moreover,the Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)SE presented>90%capacity retention over 200 and 300 cycles when the cell was tested with LiNi_(0.8)Co_(0.15)Al_(0.05)O_(2)(NCA)cathode material vs.5 and 10 mg cm^(-2)@RT.

前列腺癌患者外周血中CD4^+CD25^(high)调节性T细胞及调节因子TGF-β1和COX-2的表达

目的:通过检测前列腺癌患者以及健康志愿者外周血中CD4+CD25high调节性T细胞、TGF-β1及COX-2的表达,初步探讨CD4+CD25high调节性T细胞在前列腺癌发病机制中的作用及其与TGF-β1和COX-2的相关性。方法:应用流式细胞术检测30例前列腺癌患者治疗前后(其中前列腺癌局限组11例,非局限组19例)及20例健康志愿者外周血单个核细胞(PBMC)中CD4+CD25high调节性T细胞占CD4+T细胞的比例;应用酶联免疫吸附试验(ELISA)检测其外周血清中TGF-β1和COX-2的表达。对前列腺癌患者上述指标进行术前术后对比分析,另对CD4+CD25high调节性T细胞与TGF-β1及COX-2的相关性进行分析;并探讨上述指标在前列腺癌患者局限组和非局限组间是否存在差异性。结果:流式细胞术检测显示,前列腺癌患者治疗前PBMC中CD4+CD25high调节性T细胞占CD4+T细胞的比例为(18.32±7.49)%,高于健康志愿者对照组(7.77±1.86)%(P<0.05)。前列腺癌患者治疗后其比值为(17.34±5.87)%,较治疗前稍减低,但两者相比无显著差异(P>0.05)。ELISA检测外周血清中TGF-β1和COX-2显示,前列腺癌组分别为(215.97±55.16)ng/ml和(6.88±5.14)ng/ml,对照组分别为(149.75±47.11)ng/ml和(5.65±2.69)ng/ml;前列腺癌患者外周血清中TGF-β1的表达水平高于健康志愿者对照组(P<0.05),COX-2的表达水平与对照组无显著差异(P>0.05)。通过多重线性回归分析表明,前列腺癌患者PBMC中CD4+CD25high调节性T细胞的表达与血清中TGF-β1和COX-2的表达无显著相关。前列腺癌局限组和非局限组外周血中CD4+CD25high调节性T细胞、TGF-β1及COX-2的表达均无显著性差异(P>0.05)。结论:前列腺癌患者PBMC中CD4+CD25high调节性T细胞可能参与前列腺癌的发生,其增殖机制与血清中TGF-β1和COX-2的表达无关,可能与肿瘤本身及肿瘤局部微环境相关。

Future Changes in Extreme High Temperature over China at 1.5℃-5℃ Global Warming Based on CMIP6 Simulations

Extreme high temperature(EHT)events are among the most impact-related consequences related to climate change,especially for China,a nation with a large population that is vulnerable to the climate warming.Based on the latest Coupled Model Intercomparison Project Phase 6(CMIP6),this study assesses future EHT changes across China at five specific global warming thresholds(1.5℃-5℃).The results indicate that global mean temperature will increase by 1.5℃/2℃ before 2030/2050 relative to pre-industrial levels(1861-1900)under three future scenarios(SSP1-2.6,SSP2-4.5,and SSP5-8.5),and warming will occur faster under SSP5-8.5 compared to SSP1-2.6 and SSP2-4.5.Under SSP5-8.5,global warming will eventually exceed 5℃ by 2100,while under SSP1-2.6,it will stabilize around 2℃ after 2050.In China,most of the areas where warming exceeds global average levels will be located in Tibet and northern China(Northwest China,North China and Northeast China),covering 50%-70%of the country.Furthermore,about 0.19-0.44 billion people(accounting for 16%-41%of the national population)will experience warming above the global average.Compared to present-day(1995-2014),the warmest day(TXx)will increase most notably in northern China,while the number of warm days(TX90p)and warm spell duration indicator(WSDI)will increase most profoundly in southern China.For example,relative to the present-day,TXx will increase by 1℃-5℃ in northern China,and TX90p(WSDI)will increase by 25-150(10-80)days in southern China at 1.5℃-5℃ global warming.Compared to 2℃-5℃,limiting global warming to 1.5℃ will help avoid about 36%-87%of the EHT increases in China.

High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.

LaSrNiO_(4-λ) with K_2NiF_4 Strcture──A Highly Active Catalyst for Direct Decomposition of Nitrogen Monoxide

A series of perovskite-like mixed oxides La2-xSrxMO4±λ(M =Cu, Co,Ni; x=0,1 ) was prepared and characterized using X-ray powder diffraction. The catalytic properties of these catalysts in NO decompositiori were tested. The results showed that LaSrNiO4-λ with K2NiF4 structure is very active and stable for the decomposition of NO.

Process for improving the ladle free- opening rate for high aluminum steel in continuous casting

Steel 20Mn23AlV is a type of high aluminum steel with a very low ladle free-opening rate. The aluminum composition of 20Mn23AlV ranges from 1.6% to 2.45% ,which is significantly higher than other types of steel. According to the real condition of 40 t ladle in steel-making plant of Baosteel Special Steel Company, previous works show that the key factors affecting the ladle free-opening rate of high aluminum steel in continuous casting are：sand material, accessories baking, ladle nozzle cleaning, the process and amount of adding sand, and the rate of argon stirring during refining. Therefore, improving the ladle filler sand quality, baking all of the raw materials, controlling the addition of ladle filler sand, cleaning the ladle nozzle, and optimizing argon stirring during the refining process can resolve the problem of a low ladle free-opening rate of high aluminum steel caused by the long ladle time of liquid steel.

Layer regrouping for water-flooded commingled reservoirs at a high water-cut stage

Layer regrouping is to divide all the layers into several sets of production series according to the physical properties and recovery percent of layers at high water-cut stage, which is an important technique to improve oil recovery for high water-cut multilayered reservoirs. Dif- ferent regroup scenarios may lead to different production performances. Based on unstable oil-water flow theory, a multilayer commingled reservoir simulator is established by modifying the production split method. Taking into account the differences of layer properties, including per- meability, oil viscosity, and remaining oil saturation, the pseudo flow resistance contrast is proposed to serve as a characteristic index of layer regrouping for high water-cut multilayered reservoirs. The production indices of multi- layered reservoirs with different pseudo flow resistances are predicted with the established model in which the data are taken from the Shengtuo Oilfield. Simulation results show that the pseudo flow resistance contrast should be less than 4 when the layer regrouping is implemented. The K-means clustering method, which is based on the objec- tive function, is used to automatically carry out the layer regrouping process according to pseudo flow resistances. The research result is applied to the IV-VI sand groups of the second member of the Shahejie Formation in the Shengtuo Oilfield, a favorable development performance is obtained, and the oil recovery is enhanced by 6.08 %.

A Simple and Highly Efficient Enantioselective Synthesis of (<i>S</i>)-Rivastigmine

A highly efficient and convenient procedure for the enantioselective synthesis of (S)-Rivastigmine, a cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson’s disease, is accomplished by the treatment of versatile, readily accessible (S)-(-)-2-methyl-2-propanesulfinamide with 3-hydroxyacetophenone. This protocol provides high yield and excellent enantiomeric excess in short step synthesis.

Plastic Flow Modeling of Ti-5 Al-2 Sn-2 Zr-4 Mo-4 Cr Alloy at Elevated Temperatures and High Strain Rates

The true stress-sWain relationships of Ti-5A1-2Sn-2Zr-4Mo-4Cr（TC17） alloy with a wide range of strain rates were investigated by tmiaxial quasi-static and dynamic compression tests, respectively. Quasi- static compression tests were carried out with Instron 8874 test machine, while dynamic compression tests were performed with the split Hopkinson pressure bar （SHPB） which was installed with heating device and synchro- assembly system. The dynamic mechanical behaviors tests of TC17 were carded out from room temperature to 800 ℃ at intervals of 200 ℃ and at high sWain rates （5 500-1 9200 s-l）. The stress-strain curves considering temperature-sWain rate coupling actions were obtained. The Johnson-Cook constitutive model was developed through data fitting of the stress-sWain curves. The material constants in the developed constitutive model can be determined using isothermal and adiabatic stress-strain curves at different strain rates. The Johnson-Cook constitutive model provided satisfied prediction of the plastic flow stress for TC17 alloy.

A COMPUTER SIMULATION OF HIGH-DOSE ION IMPLANTATION INTO AMORPHOUS MATERIALS

A computer program MACA was developed for simulating high-dose ion implantation into amorphous solids. The topology of amorphous solids was modelled by adjusting the free flight path distribution between collisions, so that the radial distribution function will characterize the short - range order and long - range disorder of amorphous targets. A simulation example is given.

Manufacturing of Ultra-high Molecular Weight Polyethylene Fiber Reinforced Tape and the Loss of Strength

Due to the low density and excellent mechanical proper-ties,high performance fiber reinforced materials have aconsiderable application in the area of high technologyand dally usage.In this paper,the Ultra-high Molecu-lar Weight Polyethylene(UHMWPE)fiber reinforcedPE tape prepared with the method of powder impregnat-ion was studied.The effect of impregnate length and thetensile force of the yarn on the fiber content as well as on the strength and modulus of the tape were discussed.Calculation shows that the strength and the modulus ofthe ULMWPE fiber can keep about 85％ after it undergothe process.

A super-high angular resolution principle for coded-mask X-ray imaging beyond the diffraction limit of a single pinhole

High angular resolution X-ray imaging is always useful in astrophysics and solar physics. In principle, it can be performed by using coded-mask imaging with a very long mask-detector distance. Previously, the diffraction-interference effect was thought to degrade coded-mask imaging performance dramatically at the low energy end with its very long mask-detector distance. The diffraction-interference effect is described with numerical calculations, and the diffraction-interference cross correlation reconstruction method （DICC） is developed in order to overcome the imaging performance degradation. Based on the DICC, a super-high angular resolution principle （SHARP） for coded-mask X-ray imaging is proposed. The feasibility of coded mask imaging beyond the diffraction limit of a single pinhole is demonstrated with simulations. With the specification that the mask element size is 50 × 50 μm^2 and the mask-detector distance is 50 m, the achieved angular resolution is 0.32arcsec above about 10keV and 0.36arcsec at 1.24keV （λ = 1 nm）, where diffraction cannot be neglected. The on-axis source location accuracy is better than 0.02 arcsec. Potential applications for solar observations and wide-field X-ray monitors are also briefly discussed.

Preparation of High Molecular Weight Poly(L-lactide-co-caprolactone)(85-15)

Poly（L-lactide-co-caprolactone）（85-15）[P（LLA-CL）（85-15）] was synthesized from high purity L-lactide and e-caprolactone using tin octoate as initiator by ring-opening polymerization, and characterized by infrared spectrum and IH-NMR spectrum. The synthesized P（LLA-CL）（85-15） is a random copolymer. The influences of polymerization temperature, polymerization time, dosage of initiator and polymerization pressure on the weight average molecular weight and the polydispersity index of P（LLA-CL）（85-15） were investigated. The optimum preparation conditions of P（LLA-CL）（85-15） are： the polymerization pressure is less than 0.5 Pa, the polymerization temperature is 130 ~C, the n（M）/n（I） ratio is 8 000/1, and the polymerization time is 36 h. Under the condition, the weight-average molecular weight of prepared P（LLA-CL）（85-15） is 65.6x 104, and molecular weight distribution coefficient is 1.15.

Synthetic sensitivity analysis of high frequency radiation of 2011Tohoku-Oki(MW9.0) earthquake

Frequency-dependent rupture behavior of sub- duction zone interplate megathrust faults has been observed by back-projection method in different frequency bands （from 0.05 to 5 Hz）. It has been suggested that the down-dip region of the Tohoku megathrust radiated strongly at high frequencies （〉10 Hz） compared with that of the up-dip region. By assuming the same source tirne function of each fault patch, we perform a synthetic sensitivity analysis to compare the energy received from the shallower parts （and further way from the receiver sites） with that frona the deeper parts （and closer to the receiver sites） of the rupture. Our results indicate that regional onshore recordings are probably not adequate to constrain the presence of far-off shore high frequency radiations because of the strong attenuation of this region.

Diffusion bonding behaviour of β-γTiAl alloys containing high niobium with Ti interlayer by spark plasma sintering

High niobium β-γ TiAl alloy(HNBG) was diffusion bonded using spark plasma sintering with pure Ti as interlayer. The joint microstructural evolution, growth kinetics and mechanical properties were investigated. The joint included three diffusion zones. The β/B2 phase formed in the Zone Ⅰ, α_(2)phase in the Zone Ⅱ, and β-Ti and α-Ti phases in the Zone Ⅲ. The thickness of β/B2 phase, the average grain size of α_(2)phase and the amount of β-Ti phase increased with the increase of bonding temperature or bonding time. The growth activation energies of β/B2 and α_(2)phases were 582 and 253 kJ/mol, respectively. The joint acquired at 1000 °C, 10 min and 10 MPa showed the maximum shear strength of 308 MPa. Fracture mainly occurred along the interfaces between Zone Ⅰ and HNBG alloy, and between Zone I and Zone Ⅱ. Fracture mechanism of the joint was characterized by brittleness rupture along the phase boundary.

Ang-(1-7)exerts anti-inflammatory and antioxidant activities on high glucose-induced injury by prohibiting NF-κB-IL-1βand activating HO-1 pathways in HUVECs

Previous reports have suggested that Ang-(1-7)may have a protective effect in endothelial cells against high glucose(HG)-induced cell injury thanks to a modulatory mechanism in the NF-κB signaling pathway.In this study,we have examined whether NF-κB-IL-1βand Heme oxygenase-1(HO-1)pathways contribute to the protection of Ang-(1-7)against hyperglycemia-induced inflammation and oxidative stress in human umbilical vein endothelial cells(HUVECs).Our results indicate that time-varying exposures of HUVECs,from 1 h to 24 h,to high glucose concentrations result in an increased expression of phosphorylated(p)-p65 and HO-1 in a time-dependent manner.As an inhibitor of NF-κB,pyrrolidinedithiocarbamic acid(PDTC)suppressed IL-1βproduction induced by HG.Of note,HUVECs previously treated with Ang-(1-7)(2μM)for 30 min before being exposed to HG concentrations significantly ameliorated the HG-increased in p-p65 and IL-1βexpression;whereas obviously up-regulated the level of HO-1,along with inhibition of oxidative stress,inflammation,and the HG-induced cytotoxicity.Importantly,when HUVECs were previously treated either with PDTC or IL-1Ra for 30 min before being exposed to HG,it significantly prevented damages caused by high glucose concentrations mentioned above,while the treatment of HO-1 inhibitor Sn-protoporphyrin(SnPP)before exposure to both HG and Ang-(1-7)significantly blocked the protective effect exerted by Ang-(1-7)on endothelial cells against injuries induced by HG mentioned above.To conclude,the data of this study showed that activation and inhibition of the NF-κB-IL-1βpathway and HO-1 pathway may constitute an important defense mechanism against endothelial cell damage caused by HG concentrations.We additionally gave new evidence showing that exogenous Ang-(1-7)exerts a protective effect on HUVECs against the HG-induced cell injury via the inhibition and the activation of the NF-κB-IL-1βpathway and the HO-1 pathway,respectively.

High-Resolution Stark Spectroscopy of Ba Highly-Excited States by Diode Laser Technique

High-resolution atomic-beam laser spectroscopy has been performed to study Stark effect of Ba atom. Stark spectra have been observed at various electric fields for Ba highly excited states. The scalar polarizability of the transition from 6s5d3D2 to 5d6p3F3 at 728.0 nm and the tensor polarizability of the 3F3 level have been determined for the first time, to be αs = -89.8 (12) kHz/(kV/cm)2 and αt = -133.7 (20) kHz/(kV/cm)2, respectively.

High Strain Rate Induced Plasticity-increasing of Metallic Materials under Tension

The effect of strain rate on plasticity has been Investigat-ed for three metallic materials with dynamic tension tech-nique. A phenomenon of high strain induced plasticity -increasing was found for tested materials. The elongation of quenched 30CrMnSiNi2A is 14. 5% under 40 m/s loading rate which is more than two times of the 7 % un-der 0. 5 mm/min. This typic high strain rate induced plasticity - Increasing phenomenon is associated with adiabatic heating, strain twinning and suppression of strain - induced - phase transformation.