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Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction and insulin resistance. Islet amyloid polypeptide (IAPP) aggregation is found to induce islet β-cell death in T2DM patients. Recently, we demonstrated that yakuchinone B derivative 1 exhibited inhibitory activity against IAPP aggregation. Thus, in this study, a series of synthesized yakuchinone B-inspired compounds were tested for their anti-IAPP aggregation activity. Four of these compounds, 4e-h, showed greater activity than the lead compound 1, in the sub-μM range (IC50 = 0.7-0.8 μM). The molecular docking analysis revealed crucial hydrogen bonds between the compounds and residues S19 and N22 and important hydrophobic interactions with residue I26. Notably, compounds 4g and 4h significantly protected β-cells against IAPP-induced toxicity with EC50 values of 0.1 and 0.2 μM, respectively. In contrast, the protective activities of compounds 4e and 4f were weak. Overall, these results suggest that the compounds exhibiting IAPP aggregation-inhibiting activity have the potential to treat T2DM.

Background Few studies have examined the relationship between the amounts of heavy metal and stroke incidence. The aim of this study was to explore the relationship between levels of heavy metals, including Pb, Hg, As, and Cd, in patients with acute ischemic stroke (AIS). Methods We selected patients with first-ever AIS onset within 1 week as our study group. Healthy controls were participants without a history of stroke or chronic disease, except hypertension. The serum levels of Pb, Hg, As, and Cd in participants in the experimental and control groups were determined. All participants received a 1-g infusion of edetate calcium disodium (EDTA). Urine specimens were collected for 24 h after EDTA infusion and measured for heavy metal levels. Results In total, 33 patients with AIS and 39 healthy controls were enrolled in this study. The major findings were as follows: (1) The stroke group had a significantly lower level of serum Hg (6.4 ± 4.3 μg/L vs. 9.8 ± 7.0 μg/L, P = 0.032, OR = 0.90, 95% CI = 0.81–0.99) and a lower level of urine Hg (0.7 ± 0.7 μg/L vs. 1.2 ± 0.6 μg/L, P = 0.006, OR = 0.27, 95% CI = 0.11–0.68) than the control group. (2) No significant difference in serum Pb (S-Pb), As (S-As), and Cd (S-Cd) levels and urine Pb (U-Pb), As (U-As) and Cd (U-Cd) levels was observed in either group. Conclusions Our study found low levels of serum and urine Hg in first-ever patients with AIS, providing new evidence of dysregulated heavy metals in patients with AIS. Electronic supplementary material The online version of this article (10.1186/s12929-018-0446-0) contains supplementary material, which is available to authorized users.

Autonomic dysfunctions including impaired baroreflex sensitivity (BRS) can develop after acute ischemic stroke (AIS) and may predispose patients to subsequent cardiovascular adverse events and serve as potential indicators of long-term mortality. This study aimed to determine the potential short-term prognostic significance of BRS after AIS. All patients admitted to Kaohsiung Veterans General Hospital within 72 h after onset of first-ever AIS between April 2008 and December 2012 were enrolled. Autonomic evaluation with continuous 10-minute monitoring of beat-to-beat hemodynamic and intracranial parameters was performed within 1 week after stroke by using the Task Force Monitor and transcranial Doppler. The 176 enrolled AIS patients were divided into high-BRS and low-BRS groups. All but two enrolled patients (who died within 3 months after stroke) attended scheduled follow-ups. The high-BRS group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores at 1 and 2 weeks after stroke and at discharge, lower modified Rankin scale (mRS) scores 1, 3, 6, and 12 months after stroke, and lower rates of complications and stroke recurrence compared to the low-BRS group. This study provides novel evidence of the utility of BRS to independently predict outcomes after AIS. Furthermore, modifying BRS may hold potential in future applications as a novel therapeutic strategy for acute stroke.

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This work establishes a batch module called “integration of finite element analysis and optimum design” by taking gear systems as testing examples. This batch module consists of I-DEAS, ABAQUS/Standard and MOST software, which serve as the preprocessor, the numerical solver and the optimizer, respectively. A simple and practical method was developed, by which this module was enabled to search for contact nodes and elements and to automatically define the contact surfaces for contact analysis. A simple gear-pair system and a complete planetary gear system were successively used as testing examples for this integrated module. The module will automatically construct the geometrical model, analyze contact stress and solve for the optimal solutions when gearing parameters are input. The results are expected to enhance the technology of gear system design.

Primary intracerebral hemorrhage (ICH) occurs more commonly in Taiwan than in other western countries. Recurrence of primary ICH after a first episode is not rare. The purpose of this study is to investigate the incidence, risk factors, and prognosis of recurrent primary ICH.From the stroke registration data of Kaohsiung Veterans General Hospital (KSVGH), all patients admitted between Jan. 1999 and Dec. 2003 with the discharge diagnosis of ICH were identified. The hospital records and images of each ICH patient were carefully reviewed and the diagnosis was confirmed by one of the investigators. For those patients admitted in this study period with the diagnosis of acute primary ICH who also had past medical history of ICH, the record and image of the past admission were also obtained for review, either from KSVGH or other hospitals. Patients with ICH due to secondary causes were excluded.585 patients with primary ICH were reviewed. Among them, 34 (5.8%) patients were found to have recurrent primary ICH. The medical records of these 34 patients were obtained for further analysis. Cerebral amyloid angiopathy was diagnosed in 4 (11.7%) patients. Mean ages at the onset of the first and second hemorrhages were 64 +/- 13 and 66 +/- 13 years, respectively. The mean interval between first and second hemorrhages was 33 months (from 1 month to 10 years). The most common location of first-second bleeding was basal ganglion-basal ganglion. The mortality rate in this group was 23.5%. Fifteen (38.2%) patients became totally dependent or vegetative after the second ICH.Recurrent primary ICH is not uncommon. The main location of recurrent bleeding was basal ganglion. This may implicate hypertension as the main cause of ICH. Hypertension is an important risk factor of recurrent primary ICH. Amyloid angiopathy is another cause of recurrent primary ICH. The prognosis after the second hemorrhage is worse, while the mortality and morbidity after first ever primary ICH were 15.6% and 17.9%, respectively.