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Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.

Abstract Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Abstract A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population.Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic–clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies.Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = −6.02; 95% CI −6.50 to −5.54; I2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = −4.56, 95% CI −6.02 to −3.10; I2 = 82.6%) and lower frequency of tonic–clonic seizures (WMD = −3.32; 95% CI −4.75 to −1.89; I2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups.Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically.

Abstract Introduction To evaluate effectiveness of human urinary kallindinogenase (HUK) in patients with acute ischemic stroke (AIS) according to Chinese ischemic stroke subclassification (CISS) and analyzed risk factors of clinical efficacy. Methods In this retrospective study, 134 patients received conventional therapy were enrolled to control group, and 132 patients received HUK treatment were enrolled to HUK group. National Institute of Health Stroke Scale (NIHSS) score was used to evaluate the clinical efficacy. Multivariate analysis of risk factors was performed by using logistic regression. Results After treatment, NIHSS score of HUK group was significant lower than that of control group (p = .009). Effectiveness rate was 71.2% in HUK group, and 53.7% in control group, respectively (p = .003). The NIHSS of patients with large artery atherosclerosis (LAA) subtype in HUK group was significantly lower than that in control group (p = .005). The absence of HUK (OR = 2.75), homocysteine (OR = 0.15), and CS subtype (OR = 0.18) were risk factors for HUK clinical efficacy. Conclusions Human urinary kallindinogenase is an effective therapeutic approach for treatment of patients with AIS, especially in patients with LAA subtype. The absence of HUK, elevated homocysteine, and cardiogenic stroke subtype were risk factor for clinical efficacy of HUK.

Objectives To evaluate the effectiveness and safety of the combination of beraprost sodium (BPS) and aspirin in patients with acute ischemic stroke (AIS). Methods There were 384 patients with AIS enrolled in this single-center, retrospective study. The BPS group comprised patients who received combination therapy with BPS and aspirin, and the control group comprised those who received only aspirin. Primary measurements were glomerular filtration rate (GFR), cystatin-c (Cys-C), National Institute of Health Stroke Scale (NIHSS) score, modified activities of daily living index (MBI), modified Rankin scale (mRS), and blood coagulation indexes. Recurrence and adverse events were recorded. Results There were no significant differences in patient characteristics at baseline between the two groups. GFR and Cys-C levels increased in the BPS group compared with the control group. After treatment, the NIHSS and mRS score were significantly lower in the BPS group compared with the control group, whereas the MBI scores were significantly higher in the BPS group compared with the control group. There was no significant difference in blood coagulation between the two groups. There were no serious adverse events in either group. Conclusions Combination therapy with BPS and aspirin may be a safe and effective treatment for AIS.

Ischemic stroke refers to a focal neurological deficit attributable to the conditions created by the occlusion of an intracranial artery. We investigated how screening for abnormal glucose metabolism in acute ischemic cerebral apoplexy inpatients might be used to develop a more reasonable treatment plan and improve the prognosis of patients with acute ischemic stroke. A total of 686 patients with acute ischemic stroke, hospitalized from January 2007 to December 2010 in the neurological department of the first affiliated hospital in China Shantou Medical College, was examined in this study. We recorded each patient′s sex, age, smoking history, height, weight, blood pressure, waist circumference, random blood glucose, and fasting blood glucose, also noting if the patient had a record of having high blood sugar. In addition, we conducted a 75 g oral glucose tolerance test (OGTT) for undiagnosed diabetes patients in order to determine the status of glucose metabolism. We find that there were 368 (66.1%) cases of hospitalized cerebral vascular disease patients with abnormal glucose metabolism of which 185 (33.2%) cases are diabetes, and 183 cases (32.9%) are with impaired glucose regulation, and 189 cases (33.9%) are with normal glucose tolerance. Totally, 130 cases had been diagnosed as diabetes before their admission, accounting for 23.3% of all patients. Totally, 427 patients are without diabetes history, however, 29 diabetes cases (accounting for 15.7% of all diabetic patients) were found after a non-OGTT. We concluded that patients with acute ischemic stroke are often associated with abnormal glucose metabolism, and so OGTT screening tests will help doctors to recognize acute ischemic stroke patients.

Taking the in situ measurements as the driver, the traditional remote sensing models modeling approaches emphasize particularly on the least total errors between the modeled estimate and the measurements while ignore its local error status, which may lead to a large warp between the modeled prediction and the observation at some position. Considering such default of general approach, the present paper developed the subsection mapping retrieval algorithm (SMRA), which decomposes the mapping mechanism between the water qualities and its optical parameters into several subsection functions, and each subsection function is determined by the in situ measurements (named nodes as follows) and an interpolating function. The analysis results of subsection mapping retrieval algorithm based on Newton interposing algorithms indicate that the algorithm keeps the inversion results accuracy at nodes, and is preferably suitable for regression estimate of the complicated relationship between the parameters. Additionally, the method has a great theoretical meaning for the standardization of the sampling interval and sample number in water qualities experiments. Combined with the analysis results of the Landsat/TM imagery and the experimental data of Taihu Lake, it could be known that the SMRA is preferably suitable for describing the relationship between remotely sensed pa rameters and water qualities, especially for complicated case II water bodies such as Taihu Lake.

Eupatorium adenophorum Spreng. (EAS) is a toxic invasion plant and has caused significant economic and environmental impacts in China. The EAS has the characteristics of widely distributing and quickly spreading. The traditional detecting and supervising methods become invalid when applied for managing the spatial distribution of EAS. Based on the analyzing results of the spectrum features of EAS, the present paper tried to structure the identifying models by remote sensing. The main objective of this paper is to develop an available method for detecting and mapping the spatial distribution of EAS. The study shows that the spectrum of EAS has two reflecting peaks and one absorbing trough. The corresponding wavelengths of those peaks are 560, 730 and 674 nm, respectively. The absorption characteristics of EAS at 647 nm are that the absorbing depth is 0.504 3-1.910 3, the absorbing width is 13.778 9-17.251 8 nm and the area at the left absorption band is greater than the right, and the corresponding area ratio of left to right is 1.771 9-2.444 1. The white flowers of EAS make the reflectance higher at visible bands, and the first-order derivatives of EAS spectral show a wave peak at 420 nm. Compared with the spectral feature of other representative materials, the absorbing characteristics at 647 nm, such as absorption width and absorption depth, and the peak at 420 nm of derivatives spectral are special features of EAS spectral, which can be used as remotely sensed parameters for detecting and mapping the EAS at florescence.

The errors of the territorial parameters retrieved from remote sensing are decided by the data error and the model error. The data error is not simply added to the total errors of retrieval results. It would be reformed by the quantitative inversion model, and then, combined with the model errors and melts into the totals errors. Accordingly, during the quantitative process, taking advantage of the highest correlation coefficient or the least root mean square error as assessment standard for describing the chlorophyll a concentration vs remote sensing parameters is not reasonable. Focusing on the above problem, the study pointed out that the reason why the result of the optimized cost function is contrary with the practical is that different model has different influence on data errors. Combined with the in situ measurements of Taihu Lake, in October, 2003, it is known that due to the error magnification phenomena (TM2/TM3 algorithm is 2.28 times more than TM2/TM1 algorithm), although the regression coefficient of TM2/TM3 algorithm is higher than TM2/TM1 algorithm, the quantitative errors of TM2/TM3 algorithm are 7.938 5 microg x L(-1) more than TM2/TM1 algorithm. Moreover, the retrieval results show that distribution pattern of the results of TM2/TM3 algorithm is completely opposite to the TM2/TM1 algorithm. According to the former research achievements, the results of TM2/TM1 algorithm would be more reasonable. In summary, only when that the factor of data error is added to the optimized cost function is taken as a constrain condition in search for the optimal solution of the quantitative models, would the retrieval results be more reliable.

The complicated compositions of Case II waters result in the complex properties of spectral curves. The present paper analyzed the in situ measurements data of spectral curves, and further realized the relationships between the properties of spectral curves and suspended sediment concentration. The study found that the max peak of spectral curves was moving to the direction of shortwavelength as increasing suspended sediment concentration, namely the blue shift of wavelength; the area enclosed by spectral curve and coordinate axis in the range of sensitive bands had preferably linear relationship with the suspended sediment concentration (curve area model); the trapezoidal area model which was an approximation of curve area model could also excellently reflect those relationships, and be greatly suitable for multi-spectral satellite imagery retrieval such as LandSat/TM, MODIS and so on. The inversion results of trapezoidal area model for LandSat/TM imagery on October 27, 2003 in Taihu Lake showed that the suspended sediment concentration ranged from 30 to 80 mg x L(-1), the distribution pattern was higher in the west, south and central lake and lower in the east lake; compared with the in situ measurements in the regions, and the relative error of retrieval model was 6.035%.