The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Objective To construct a transparent and visualized bionic model of human utricle and explore the biomechanical response of the utricle to linear acceleration.Methods Using three-dimensioanl(3D)printing technology and PVA-gelatin composite hydrogel fabrication method,a visual physical model of the utricle with a ratio of 10∶1 to the human body was successfully prepared.The biomechanical response of the utricle macula was investigated by varying acceleration and direction stimulation experiments.Results Under 1-5 Hz sinusoidal reciprocating linear excitation,the response amplitude of the bionic macula increased from 4.11 μm to 48.82 μm.The response amplitude of the bionic macula increased linearly with the acceleration.In addition,the macula showed deformation differences in response to acceleration in a specific direction.Conclusions The bionic utricle model prepared in this study can accurately simulate the working mechanism of human utricle,which is expected to provide a new way for the pathological study of vestibular dysfunction and expand a new direction for the application of bionic technology in the field of biomedical engineering.

Objective To construct a transparent and visualized bionic model of human utricle and explore the biomechanical response of the utricle to linear acceleration.Methods Using three-dimensioanl(3D)printing technology and PVA-gelatin composite hydrogel fabrication method,a visual physical model of the utricle with a ratio of 10∶1 to the human body was successfully prepared.The biomechanical response of the utricle macula was investigated by varying acceleration and direction stimulation experiments.Results Under 1-5 Hz sinusoidal reciprocating linear excitation,the response amplitude of the bionic macula increased from 4.11 μm to 48.82 μm.The response amplitude of the bionic macula increased linearly with the acceleration.In addition,the macula showed deformation differences in response to acceleration in a specific direction.Conclusions The bionic utricle model prepared in this study can accurately simulate the working mechanism of human utricle,which is expected to provide a new way for the pathological study of vestibular dysfunction and expand a new direction for the application of bionic technology in the field of biomedical engineering.

Diabetic retinopathy(DR)is one of the most common microvascular complications of diabetes and has become one of the leading causes of blindness and visual impairment in diabetes patients.The pathogenesis of DR is multifaceted,involving inflammation,oxidative stress,neurovascular abnormalities,and other factors that present potential targets for disease management interventions.Currently,anti-vascular endothelial growth factor(VEGF)drugs serve as the primary treatment for advanced stages of DR when irreversible neurovascular damage and visual impairment have occurred.Additionally,some patients show poor or no response to anti-VEGF treatment.There is a lack of early intervention options for the initial phases of the disease.Therefore,there is an urgent need to develop novel local or systemic therapies based on the underlying mechanisms of DR to enable early prevention and treatment with the aim of preserving patients' vision.Medications targeting various pathways including anti-inflammatory agents(corticosteroids and nonsteroidal anti-inflammatory drugs),neurotrophic and neuroprotective drugs,drugs modulating biochemical pathways,antioxidant phytochemicals,and gene therapy can complement each other in terms of therapeutic effects to benefit a larger number of individuals affected by DR.This article reviews previous research reports on the pathogenesis,drug treatment methods,and potential therapeutic targets associated with DR in order to provide guidance for clinical practice.

Objective To explore the biomechanical responses of the cupula of the human semicircular canal to three basic rotational perception processes.Methods A one-dimensional visual semicircular canal model was successfully fabricated using three-dimensional printing and hydrogel physical cross-linking technologies,and the response deformation of the cupula was explored by applying constant angular velocity,constant angular acceleration,and sinusoidal oscillation stimulations.Results The time constant of the biomimetic semicircular canal model was stable at approximately 3 s and close to the human time constant.The displacement deformation of the ampullary cupula was proportional to the angular acceleration applied.Under sinusoidal oscillation stimulation of 0.07-5.00 Hz,the gain of the semicircular canal increased from 1.54 um/° rises to 42.34 μm/°,but the phase difference decreased from 109.72° to 11.27°.Conclusions The biomimetic semicircular canal model prepared in this study can accurately simulate the working mechanism of the human semicircular canal and is expected to play a role in mechanism research and disease diagnosis of the human vestibular semicircular canal.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na⁺/H⁺ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.
Animals ; Diabetes Mellitus ; Diabetes Mellitus, Type 2/drug therapy* ; Glucose ; Humans ; Mice ; Myocardial Infarction/metabolism* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Ventricular Remodeling

Objective: To analyze the relationship between daily behavior and self-perceived academic performance among students in Jiangxi, and to provide a scientific basis for developing health behavior among adolescents and children. Methods: By using stratified cluster sampling, 12 primary and secondary schools from six counties of Jiangxi Province were selected, and a total of 2 284 students were investigated with questions including breakfast consumption, number of days participating in sports activities (≥45 min) and the average screen time during the past 7 days. Regression analysis was carried out by using ordered multi-classification logistic. Results: Of the 2 284 students surveyed, 1 374(60.16%) perceived their academic performance as very good or good, 613 (26.84%) and 297(13.00%) perceived as moderate or poor. Primary school, having breakfast every day, not playing on mobile or computer during weekday was positively associated with higher self-perceived academic performance (OR=0.50, 0.57 and 0.64, respectively, P<0.05), no sports activities ≥45 min during the past 7 d was associated with poor(OR=1.57, P<0.01). Among the 2 284 students, 67.43% students ate breakfast every day in the past 7 d, 75.39% students did not play mobile phones or computers at school, 40.89% students did not participate in sports activities (≥45 min). Conclusion Breakfast skipping and insufficient physical exercise shows adverse effects, and no/limited screen time during weekdays shows positive effects on academic performance. Intervention of visky behaviors should to carried out from different perspectives to promote the develpment of the health habits among students.

Objective To analyze the risk factors that affect the early recurrence (recurrence occurring within 3 months after surgical resection) of hepatocellular carcinoma (HCC), and to discuss the risk factors influencing the survival after hepatectomy. Methods The clinical data of 257 HCC patients, who were admitted to authors' hospital during the period from January 1, 2007 to March 31, 2014 to receive cTACE within 3 months after surgical resection of hepatocellular carcinoma, were retrospectively analyzed. According to DSA findings (lipiodol CT scan was performed in part of patients with undetermined diagnosis), the patients were divided into recurrence group and non-recurrence group. By using univariate analysis and multiple logistic regression analysis, the correlation of the clinical and pathological data with the early recurrence was analyzed. The patients were followed up, the survival time was recorded. The relationship between patient's clinical data and postoperative survival was evaluated. Results ① Of the 257 patients, early recurrence was detected in 150 patients (58. 4％, recurrence group) and no recurrence was observed in 107 patients (41. 6％, non-recurrence group). ②The presence of satellite nodules and the integrity of tumor encapsulation were two independent factors associated with the postoperative residual lesions. ③The maximum diameter of the tumor, Edmondson grade and the vascular cancer thrombus were the independent risk factors affecting survival. ④The median survival time of patients in recurrence group was markedly shortened than that of patients in non-recurrence group (39 months vs. 93 months). Conclusion The early recurrence (within 3 months after resection) of hepatocellular carcinoma is associated with the presence of satellite nodules and the integrity of tumor encapsulation. The survival of patients after hepatectomy is related to the maximum diameter of the tumor, Edmondson grade and the vascular cancer thrombus. The median survival time in patients having early recurrence is significantly shortened than that in patients having no early recurrence. (J Intervent Radiol, 2018, 27: 215-222)

The aim of this study was to identify antigens for a vaccine or drug target to control rabbit coccidiosis. A combination of 2-dimensional electrophoresis, immunoblotting, and mass spectrometric analysis were used to identify novel antigens from the sporozoites of Eimeria stiedae. Protein spots were recognized by the sera of New Zealand rabbits infected artificially with E. stiedae. The proteins were characterized by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) analysis in combination with bioinformatics. Approximately 868 protein spots were detected by silver-staining, and a total of 41 immunoreactive protein spots were recognized by anti-E. stiedae sera. Finally, 23 protein spots were successfully identified. The proteins such as heat shock protein 70 and aspartyl protease may have potential as immunodiagnostic or vaccine antigens. The immunoreactive proteins were found to possess a wide range of biological functions. This study is the first to report the proteins recognized by sera of infected rabbits with E. stiedae, which might be helpful in identifying potential targets for vaccine development to control rabbit coccidiosis.
Coccidiosis* ; Computational Biology ; Eimeria ; Electrophoresis ; HSP70 Heat-Shock Proteins ; Immunoblotting ; Mass Spectrometry ; Rabbits ; Sporozoites