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.

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.

Tectono-Sedimentary History of Southeastern Coast Region,China:a Synthesis

According to the ideas and concepts of systems dynamic of continent structure, using previous information related to the study area, combining analyses on orogenic belt, basin and magmatic rock, the present paper synthesizes the tectono - sedimentary development of southeastern coast region, China, with special emphasis on the mountain making, basining and magmatic activity. The tectonic evolution after Late Caledonian orogeny was dominated by alternating rifting and converging, subsiding and uplifting, mountain making and basining in central and southern parts of southeastern China and the adjacent regions to the east and west. Seventeen geologic events , nine events of plate or terrain convergence , and continental crust accretion , as well as eight events of intracontinental rifting and basin faulting , are closely related to the tectonic and sedimentary evolution of the study area . The accompanied intense and frequent sedimentation , folding , faulting , magmatism and ore- forming process allowed huge coal , multimetal and potential petroleum source rocks to form in local depressions throughout the Caledonian to Himalavan time .

Mechanoresponsive MiR-138-5p Targets MACF1 to Inhibit Bone Formation

Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.

The 30–60-day Intraseasonal Variability of Sea Surface Temperature in the South China Sea during May–September

This study investigates the structure and propagation of intraseasonal sea surface temperature（SST） variability in the South China Sea（SCS） on the 30-60-day timescale during boreal summer（May-September）. TRMM-based SST, GODAS oceanic reanalysis and ERA-Interim atmospheric reanalysis datasets from 1998 to 2013 are used to examine quantitatively the atmospheric thermodynamic and oceanic dynamic mechanisms responsible for its formation. Power spectra show that the 30-60-day SST variability is predominant, accounting for 60% of the variance of the 10-90-day variability over most of the SCS. Composite analyses demonstrate that the 30-60-day SST variability is characterized by the alternate occurrence of basin-wide positive and negative SST anomalies in the SCS, with positive（negative） SST anomalies accompanied by anomalous northeasterlies（southwesterlies）. The transition and expansion of SST anomalies are driven by the monsoonal trough-ridge seesaw pattern that migrates northward from the equator to the northern SCS. Quantitative diagnosis of the composite mixed-layer heat budgets shows that, within a strong 30-60-day cycle, the atmospheric thermal forcing is indeed a dominant factor, with the mixed-layer net heat flux（MNHF） contributing around 60% of the total SST tendency, while vertical entrainment contributes more than 30%. However, the entrainment-induced SST tendency is sometimes as large as the MNHF-induced component, implying that ocean processes are sometimes as important as surface fluxes in generating the30-60-day SST variability in the SCS.

Prevalence and Years Lived with Disability for Dental Caries among Children Aged 0-14 Years in China, 1990-2016

The estimate of dental caries among Chinese children at the microscale level using standard methodology remains unclear. In this study, we assessed and analyzed the disease burden of childhood dental caries in China by extracting data from the Global Burden of Disease, Injuries, and Risk Factors Study 2016 （GBD 2016）. In 2016, the number of cases, prevalence, years lived with disability （YLD）, and age-standardized YLD rate of dental caries was 93.0 million, 43.0%, 32,200 person years, and 14.8 per 100,000, respectively. Across 33 provincial units, the disease burden was highest in Hubei （YLD rate 28.6 per 100,000）, lowest in Macao （9.1 per 100,000）, while geographical clustering was not observed. Compared with 1990, the prevalence in 2016 decreased from 46.8% to 43.0%, and the YLD rate decreased from 16.5 per 100,000 to 14.8 per 100,000. Given the slight decrease in dental caries burden, the prevalence and disease burden remained high among Chinese children. Strategies for addressing the spatial inequity of childhood dental caries require geographical targeting.

Intact Polar and Core Tetraether Lipids in Sediments from the Haiyang 4 Cold-seep of the Northern South China Sea and their Implications

A number of cold seeps have been discovered in the northern South China Sea(SCS) including the Haiyang 4 cold-seep area where Core 973-5 was collected. Intact polar lipids(IPLs) and core lipids(CLs) were analyzed separately in sediments from Core 973-5. The most abundant lipid biomarkers were isoprenoidal GDGTs(iso GDGTs), with Crenarchaeol and GDGT-0 predominating. IPL-iso GDGTs and CL-iso GDGTs were mainly derived from Thaumarchaeota. IPL-iso GDGTs were mainly produced and retained in situ thus containing most of the in situ microbiological information. Branched GDGTs were predominantly derived from generated in marine production, and mixed with some terrestrial inputs. All IPLs groups presented a high value in the sulfate-methane transition zone(SMTZ). Furthermore, IPL and CL-MI, IPL-R;showed the highest values within the SMTZ, while IPL and CL-R;had the lowest values at the SMTZ, suggesting that the contribution of Methanophila and methanogenic to GDGTs increased, while the contribution of ammonia-oxidizing Archaea to GDGTs decreased at the SMTZ.

2016-2020年国家自然科学基金中医骨伤科学项目资助概况及热点分析

目的探讨2016-2020年国家自然科学基金中医骨伤科学资助总体情况及主要研究方向,为中医骨伤科学科研的进一步发展提供参考依据。方法通过八爪鱼采集器(V8.2.2.111911)软件采集国家自然科学基金2016-2020年申请代码为H.3110(中医骨伤科学)资助项目所有信息,采用Excel2016数据透视表统计分析项目资助数量、金额、依托单位、省份等,并通过PyCharm 2021.2.2(Community Edition)软件撰写jieba分词代码及Word2016的宏代码程序对项目名称进行分词,并将疾病类型、具体干预措施、项目名称词频结果导入Word Art官方网站进行在线热点词云图绘制以分析研究热点。结果2016-2020年国家自然科学基金中医骨伤科学领域资助项目数量、金额总体平稳略上升;项目类型以面上项目和青年科学基金项目为主,获资助项目的依托单位以中医高等院校为主,立项资助总体布局呈现出地域发展不平衡的态势。项目名称、关键词词云分析表明,项目关注的疾病主要包括“膝骨关节炎”(34次)、“骨质疏松症”(19次)、“脊髓损伤”(17次)、“骨关节炎”(14次)、“激素性股骨头坏死”(13次)、“绝经后骨质疏松症”(10次)等,干预措施主要包括“补肾活血方”(15次)、“补肾活血法”(9次)、“补肾中药”(9次)、“补肾法”(8次)、“中药”(7次)、“补肾活血中药”(6次)等。项目名称词云分析表明,热点词汇主要包括“机制”“调控”“信号通路”“自噬”“miRNA”“lncRNA”“骨髓间充质干细胞”“组学”等。结论2016-2020年国家自然科学基金资助的中医骨伤科学领域研究有学科交叉特点,学术资源向中医高等院校集中明显,呈现不均衡发展趋势,重点研究慢性筋骨病,补肾活血是治法研究热衷领域。

Comparisons between glucose analogue 2-deoxy-2-(^(18)F)fluoro-D-glucose and ^(18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM: To compare 2-deoxy-2-(18F)fluoro-D-glucose(18F-FDG) and 18F-sodium (18F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent 18F-FDG and 18F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity (Se), specificity (Sp), overall accuracy, positive and negative predictive values, error rate, and Youden’s index. McNemar’s χ2 test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the co-registered CT (sclerotic, lytic, mixed, no-lesions) and the divergent site of disease (skull, spine, ribs, extremities, pelvis). The impact of adding 18F-NaF PET/CT to the work-up of patients was also measured in terms of change in their management due to 18F-NaF PET/CT findings.RESULTS: The two imaging methods of 18F-FDG and 18F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively (McNemar’s χ2 = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis (McNemar’s χ2 = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, 18F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis (P < 0.002) and vertebral localizations (P < 0.002); 18F-NaF PET/CT was more accurate in detecting sclerotic (P < 0.005) and rib lesions (P < 0.04). 18F-NaF PET/CT led to a change of management in 3 of the 45 patients (6.6%) by revealing findings that were not detected at 18F-FDG PET/CT.CONCLUSION: 18F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of 18F-NaF PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of 18F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings (i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative 18F-FDG PET and conventional imaging).

Antimicrobial Resistance,Virulence Profile,and Molecular Characterization of Listeria monocytogenes Isolated from Ready-to-eat Food in China,2013-2014

We aimed to investigate the potential pathogenic profile and antibiotic resistance of Listeria monocytogenes isolated from ready-to-eat food in China.Antimicrobial resistance was determined by broth microdilution following the Clinical and Laboratory Standards Institute protocol Molecular serotyping,virulence,and resistance genes were identified using PCR.Multi-locus

Reconstruction of Sub-Decadal Winter Half-Year Temperature during 1651-2010 for the North China Plain Using Records of Frost Date

We extracted 374 pieces of records of frost date from historical documents. Using these records, we reconstructed winter half-year (October to next April) temperature series, with a resolution of 5-year, for the North China Plain during 1651-2010. The results show that the temperature changes in the North China Plain were divided into four phases. With the reference period of 1951-1980, two cold phases, 1651-1700 and 1781-1900, have cold anomaly of 0.83°C and 0.60°C respectively. However, between the two cold phases, 1701-1780 was a relative warm phase with the cold anomaly of 0.36°C referring to the mean of 1951-1980. After the 1900, the climate came into a warm phase. The mean temperature of 1901-2010 was 0.11°C higher than the mean of 1951-1980. During 1651-2010, the 1996-2000 is the warmest 5-year with the warm anomaly of 1.25°C than that of the reference period of 1951-1980.

Genetic Relationship of the 1780-1760 Ma Dykes and the Coeval Volcanics in the Lvliang Area, North China

The 1780-1760 Ma Taihang dyke swarm and the coeval Xiong’er volcanic province are the most widespread magmatic events occurring post the amalgamation of the two North China cratons.It has been debated whether

Multi-fractal Behaviors of Relative Humidity over China

The multi-fractal ity over China are studied behaviors of relative humid using the multi-fractal de trended fluctuation analysis （DFA） method. Three multi fractal parameters （the spectrum width Aa, the asymmetry Aaas, and the long-range correlation exponent a0） of the singularity spectrum are introduced to quantify the multi-fractal behaviors. The results show that multi-frac tality exists in daily humidity records over most stations in China and is mainly due to the broad distribution of the probability density of the sequence values. Strong multi fractal behaviors over some stations in the Yunnan, Guangdong, and Inner Mongolia provinces are obvious. These behaviors are mainly caused by different long range correlations between large and small fluctuations. The asymmetry of the singularity of relative humidity records is weak, except for a small number of stations in the far east and west of China, where the singularity spec trum is left-skewed. Finally, the long-range correlations in North China are stronger than those in South China, which indicates better predictability in North China. By studying the parameters of the multi-fractal spectrum, various data of long-range power law correlations of the relative humidity records are obtained, which may pro vide theoretical support for climate prediction.

First Asia-Pacific Forum on Andrology 17-21 October 2002, Shanghai, China

Honorary President: Jie-Ping WuChairman: Shao-Zhen QianSecretary General: Hong XiaoInternational Advisory CommitteeChairman: Geoffrey MH WaitesVice-Chairman: Ilpo Huhtaniemi, Ying-Lu GuoMembers: Hector Chemes, Rune Eliasson, Louis JG Gooren, Carlos R Morales, Wolf-Bernhard Schill, Fred CW Wu

The 4th International Exhibition on Refractories, Industrial Ceramics and Furnaces(RCF Expo'2003)Beijing, China, April 15-17, 2003In conjunction with China Refractories Seminar' 2003-Technology and Markets

Organizers and Sponsors: China Association of Refractories Industry The Chinese Society for Metals The Chinese Ceramic Society

Mechanism of "Epimedium-Cistanche deserticola" in the treatment of breast cancer with bone metastasis

Objective:"Epimedium - Cistanche deserticola" is a kind of kidney tonifying drug commonly used in the treatment of breast cancer bone metastasis, which has good clinical effect, but the pharmacological mechanism has not been fully clarified. Methods: In this study, the network pharmacology and bioinformatics technology were used to explore the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis. TCMSP, TCM database@Taiwan and TCMID databases were used to screen the main effective components of the drug. Swiss Target Prediction and STITCH databases were used to search the potential target of action of Epimedium and Cistanche deserticola. Genecards, OMIN and Drugbank databases were used to search the cause of bone metastasis of breast cancer. The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis, A visualized network of "drug - component - target - signaling pathway" was constructed by using the software of Cytoscape 3.6.0, and the core genes were screened out. Results: The study found that there are 30 main effective components of Epimedium and Cistanche deserticola, and 544 genes are involved in the potential therapeutic targets, among which 101 genes are potential targets of Epimedium and Cistanche deserticola in the treatment of breast cancer bone metastasis. Through the analysis of GO and KEGG pathways, we found that the mechanisms involved in antitumor, osteoblast differentiation, osteoclast apoptosis and regulation of bone microenvironment, such as apoptosis, osteoclast differentiation, PI3K-Akt, HIF-1 signaling pathway, T cell receptor signaling pathway, etc. TP53, VEGFA, AKT1, EGFR, SRC, CCND1, MAPK3, ESR1 may be the key genes in the treatment of breast cancer bone metastasis. Conclusion: In this study, the network of "drug - component - target- signaling pathway" was constructed through network pharmacology, and it was found that the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis involves multiple targets and pathways, which is conducive to guiding clinical medication.

Differential interformational velocity analysis as an effective direct hydrocarbon indicator under velocity reversal conditions,an example from the anomalously high temperature and over-pressured DF1-1 Gas Field in the Yinggehai Basin,South China Sea

In the DF1-1 Gas Field in the Yinggehai Basin, South China Sea, the velocity-depth plot and velocity spectra show significant variations from a linear trend, exhibiting a distinct reversal phenomenon. Velocity parameters derived from velocity spectral analysis of the seismic data and sonic logs indicate that the interval velocity reverses below 2,100 m (2.2 s two-way time (TWT)) in the DF1-1 Gas Field. Some direct hydrocarbon indicators (DHIs) models developed for the shallow strata cannot be simply applied to the moderately to deeply buried strata for direct exploration target recognition because the velocity reversal has caused the middle-deep gas reservoirs to exhibit a moderate or weak seismic amplitude. The hydrocarbon indicator method of “Differential Interformational Velocity Analysis (DIVA)” with the aid of other hydrocarbon indicating techniques was employed to effectively identify DHIs in the middle-deep strata under velocity inversion. The result has shown that the DIVA technique can be effectively used as a DHI in both the shallow and the middle-deep strata in the study area with the shallow strata characterized by Type I DIVA anomaly and the middle-deep strata characterized by the Type II DIVA anomaly.