Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective To investigate the clinical application value of longitudinal peak strain( LPS ) and peak strain dispersion ( PSD ) in evaluating left ventricular systolic function and synchrony in patients with essential hypertension . Methods Fifty‐five patients with essential hypertension were enrolled , including 30 patients with non‐left ventricular hypertrophy ( NLV H ) , 25 patients with left ventricular hypertrophy ( LV H ) , at the same time , 30 healthy volunteers were selected as the control group . Echocardiography was performed in all three groups ,and two‐dimensional dynamic images of the left ventricular apical four‐chamber ,three‐chamber ,and two‐chamber′s long‐axis view s were collected for three consecutive cardiac cycles . T he myocardial layer‐specific strain was used to measure the LPS of the left ventricular myocardium of subendocardium ,the middle layer ,the subepicardium ,and the myocardial strain and the PSD of the w hole myocardial layers . Correlation analysis and ROC curve analysis were performed . Results T he LPS in the control group ,NLV H group and LV H group were decreased in turn from inner to out myocardial layers . Compared with the control group , the LPS in the subendocardial , middle , subepicardial ,and w hole myocardial layer of NLV H group were decreased ( P ＜ 0 .05 ) , and the subepicardial myocardial LPS was slightly lower than that in the control group ,the difference was not statistically significant ( P ＞ 0 .05 ) . T he LPS in the subendocardial , middle , subepicardial ,and whole myocardial layer of LV H group were all reduced ( P＜0 .05) . Between the NLV H group and LV H group , the declines of the LPS in the subendocardial and middle layer in the LV H group were statistically significant ( P ＜0 .05) ,the LPS in the subepicardial layer and the w hole myocardial layer had no significant difference ( P ＞0 .05) . Compared with the control group ,the PSD of the NLVH group and the LVH group increased ( P ＜ 0 .05 ) . Compared with the NLV H group ,the PSD of the LV H group increased ( P ＜0 .05) . Inter‐ventricular septum thickness ( IVSd) and the LPS in the subendocardial ,middle ,subepicardial , and w hole myocardial layer were negatively correlated ( r ＝ －0 .537 ,－0 .518 ,－0 .266 ,－0 .471 ; all P ＜0 .05) , left ventricle posterior wall thickness ( LVPWd ) and the LPS in the subendocardial , middle , subepicardial ,and whole myocardial layer were negatively correlated ( r ＝ －0 .539 , －0 .524 , －0 .283 ,－0 .478 ;all P ＜0 .05) . T he area under the ROC curve ( AUC) of the LPS in the subendocardial ,middle , subepicardial ,and w hole myocardial layer and PSD for the diagnosis of hypertension were 0 .685 ,0 .652 , 0 .510 ,0 .623 ,0 .995 ,respectively . T he cut‐off values were －21 .70% ,－18 .90% ,－16 .95% ,－19 .45% , 46 .50 ms , and the sensitivities were 94 .4% , 83 .3% , 77 .8% , 94 .4% , 100% , respectively , and the specificities were 47 .8% ,52 .2% ,39 .1% ,39 .1% ,95 .7% ,respectively . Conclusions T he layer‐specific strain can quantitatively evaluate myocardial longitudinal strain in patients with essential hypertension , provide a non‐invasive test for early diagnosis of hypertensive heart disease ,and the evaluation of left ventricular myocardial stratification . PSD for evaluating primary synchronous changes in left ventricular myocardial contraction in patients with hypertension has certain advantages .

Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound exhibited the most potent potency against EBOV with an IC value of 5.29 μmol/L and an SI value of over 37.8. Further anti-EBOV assay of identified its high effectiveness, and anti-MARV assay of suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.

OBJECTIVE:To optimize the extraction technology of caffeic acid in Laggera alata,and establish a method for its content determination. METHODS:The caffeic acid in L. alata was extracted by reflux extraction. Using extraction content as inves-tigation index,orthogonal test was used to investigate the effects of ethanol volume fraction,material-liquid ratio and extraction time on caffeic acid,and the extraction technology conditions were optimized. HPLC was adopted to determine the content of caffe-ic acid in 10 batches of L. alata from different areas,using caffeic acid as reference substance,at wavelength of 320 nm. RE-SULTS:The optimized extraction technology conditions were as follows as ethanol volume fraction of 10%,material-liquid ratio of 1 : 40 and extraction time of 3 h. Under the condition,verification test for caffeic acid was carried out,and the average content of caffeic acid in L. alata was 0.5211 mg/g(RSD=1.18%,n=3). The content of caffeic acid in 10 batches of L. alata from dif-ferent areas ranged in 0.3752-0.7766 mg/g,and the content showed great differences. CONCLUSIONS:The content of caffeic ac-id in L. alata is related to area and harvest season. The caffeic acid extration by optimized technology shows good reproducibility;and the established method for content determination is stable and feasible.

Objective To discuss the value of video -assisted thoracoscope technology in diagnosis and treatment of thoracic trauma .Methods Form January 2009 to December 2013, a retrospective analysis was carried out on 43 patients with thoracic trauma .All the patients were treated with video -assisted thoracoscope technology . Results The procedure were successful and all the patients were cured out of hospital .Conclusion It is wide oper-ation indication, little harm, definite treapeutic effect, little complication and fast recovered to treat the patient with thoracic trauma using video -assisted thoracoscope technology , and it is a good choice for diagnosis and treatment in thoracic trauma.

LPS stimulation of macrophages production of IFN-beta plays a key role in innate immunity defending the microbial invasion. In this study, the effect of S632A3 promoting LPS-induced IFN-beta production and the underlying mechanism were investigated, mRNA level was measured by real-time PCR, cytokine production was determined by ELISA, GSK-3beta activity was investigated by kinase assay, protein phosphorylation and expression were evaluated by Western blotting. The results revealed that S632A3 significantly augmented IFN-beta production by LPS-stimulated macrophages. S632A3 inhibition of the activation of GSK-3beta, reduced the threonine 239 phosphorylation of transcription factor c-Jun but increased the total level of c-Jun in LPS-stimulated macrophages. Moreover, small interfering RNA-mediated knockdown of c-Jun level abrogated the ability of S632A3 to augment IFN-beta. The study thus demonstrates S632A3 being a new anti-inflammation lead compound and provides a molecular mechanism by which S632A3 promoted LPS-induced IFN-beta production in macrophages through inhibiting the activation of GSK-3beta.