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Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38–55, range 18–60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients.

Accumulating evidence suggests that chronic metformin posttreatment offers potent neuroreparative effects against acute brain injury. However, in previous studies, metformin was not initially administered beyond 24 h postinjury, and the effects of delayed metformin treatment in traumatic brain injury (TBI) and other types of acute brain injury and the related mechanisms are unclear. To test this, male C57BL/6 mice received once daily metformin treatment (20, 50 or 100 mg/kg/d, i.p.) at day 1–14, day 1–2, day 1–10, day 3–10, day 5–12 or day 5–28 after cryogenic TBI (cTBI). The results showed that 100 mg/kg/d metformin administered at day 1–14 postinjury significantly promoted motor functional recovery in the beam walking and gait tests and reduced the infarct volume. Metformin (100 mg/kg/d) administered at day 1–10 or day 3–10 but not day 1–2 or day 5–12 after cTBI significantly improved motor functional outcomes at day 7 and 14, and reduced the infarct volume at day 14. Interestingly, the therapeutic time window was further expanded when the duration of metformin treatment starting at day 5 postinjury was extended to 2 weeks. Furthermore, compared with cTBI, the administration of metformin at day 3–10 or day 5–28 after cTBI significantly elevated the expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and growth associated protein 43 (an axonal regeneration marker) and the number of vascular branch points and decreased the area of glial scar and the number of amoeboid microglia in the peri-infarct area at day 14 or 28 postinjury. The above beneficial effects of metformin were blocked by the intracerebroventricular injection of the AMPK inhibitor compound C (40 μg/mouse/d). Our data provide the first evidence that metformin has a wide therapeutic time window for at least 5 days after cTBI, during which it can improve functional recovery by promoting tissue repair and inhibiting glial scar formation and microglial activation in a central AMPK-dependent manner.

This study aimed to investigate whether inhibition of glucagon-like peptide-1 (GLP-1) on pressure overload induced cardiac hypertrophy and apoptosis is related to activation of ATP sensitive potassium (KATP) channels. Male SD rats were randomly divided into five groups: sham, control (abdominal aortic constriction), GLP-1 analog liraglutide (0.3 mg/kg/twice day), KATP channel blocker glibenclamide (5 mg/kg/day), and liraglutide plus glibenclamide. Relative to the control on week 16, liraglutide upregulated protein and mRNA levels of KATP channel subunits Kir6.2/SUR2 and their expression in the myocardium, vascular smooth muscle, aortic endothelium, and cardiac microvasculature. Consistent with a reduction in aortic wall thickness (61.4 ± 7.6 vs. 75.0 ± 7.6 μm, p

Glial scar impedes axon regeneration and functional recovery following traumatic brain injury (TBI). Although it has been shown that rapamycin (a specific inhibitor of mammalian target of rapamycin) can reduce astrocyte reactivation in the early stage of TBI, its effect on glial scar formation has not been characterized in TBI and other acute brain injury models. To test this, ICR mice received daily administration of rapamycin (0.5 or 1.5 mg/kg, i.p.) beginning at 1 h after cryogenic TBI (cTBI). The results showed that at 3 d post-injury, 1.5 mg/kg rapamycin increased cTBI-induced motor functional deficits and infarct size, and attenuated astrocyte reactivation in the ipsilateral cortex, while 0.5 mg/kg rapamycin did not worsen brain damage and only slightly attenuated astrocyte reactivation. Furthermore, at 7 and 14 d after cTBI, 0.5 mg/kg rapamycin group showed a better motor functional performance than cTBI group. At 14 d post-injury, 0.5 mg/kg rapamycin significantly reduced the area and thickness of glial scar and chondroitin sulfate proteoglycan expression, accompanied by decreased expression of p-S6 and enhanced expression of growth associated protein 43 (an axon regeneration marker) in the region of glial scar. Our data suggest that long-term treatment with rapamycin can inhibit glial scar formation after cTBI, which may be involved in the mechanisms of increased axon regeneration and improved neurological functional recovery, and low-dose rapamycin may be more beneficial for such a therapy.

On the basis of calculation of velocity and acceleration in multi-rigid body dynamics,velocity and acceleration formulas of wheel center are established when dynamic equations of vehicle are built. Adams software is used to test correction of the method ,demonstrating high accuracy of the way， which provide theoretical basis for dynamics model of vehicle.

This paper proposes a new description method of truss structure based on adjacent matrix and the expression of element stiffness matrix (ESM) containing the joint number. Furthermore a procedure is also given for obtaining a general total stiffness matrix (GTSM) by using the method of large domain transformation matrix (LDTM). GTSM can reduce the difficulty in designing variable geometry trusses.

Based on international standards for Electric Navigational Chart in a wide variety of standard materials, such as fairways, navigation lines, beacons, buoys, wrecks, and so on, up to 180 species, and different object has different standard display. Display symbols of some objects can be determined according to category attribute or shape attribute, but some other have to be determined based on the combination of category attribute and shape attribute. In addition, there are both objects with simple and complex boundaries so it will be very important to determine a complex corresponding relationship between objects and symbols in the symbol library of electric navigational chart. On the basis of analyzing international standards for Electric Navigational Chart, this paper analyzes the corresponding relationship between objects and symbols, proposes an indexing establishment process between symbols and objects, and implemented the indexing of the symbols in Electric Navigational Chart.

The electronic chart symbol library is the important component of electronic chart display and expression. The point symbols, line symbols and fill patterns of the electronic chart symbol library are a kind of map language which is used to mark the ocean geographic elements and navigation signals, and they are the major expression of the chart. Currently GIS is not compatible with the electronic chart, and the GIS software can't support the electronic chart display in accordance with international standards. In that case, we must build the symbol library which is in accordance with the electronic chart schema requirements. Based on the study of international electronic chart specifications, this paper provides a method of building the electronic chart symbol library which is based on ArcGIS platform and in line with IHO S-52 specifications, and builds a set of integrated electronic chart symbol library.

Dofetilide (DOF), a novel Class III antiarrhythmic drug, prolongs the action potential duration (APD) and shows a positive inotropic effect in guinea pig papillary muscle. The present experiments were designed to study the positive inotropic effect of DOF on rat ventricle and explore its possible mechanism(s). Hearts from male Wistar rats (260–320 g) were divided into five groups and perfused in Langendorff mode. Ventricular myocytes were enzymatically isolated from male Wistar rats. Whole-cell voltage-clamping technique was used to test the Na+–Ca2+ exchange (NCE) current (I NCX); Calcium transients and cell shortening provoked by field stimulation or using calcium current command waveform were observed synchronously with an ionic imaging system. DOF (0.03–1.0 μM) increased left ventricular function in isolated rat hearts in a concentration-dependent manner. DOF (0.03–1.0 μM) also concentration-dependently increased both inward and outward I NCX in isolated rat ventricular cells. The EC50 values of DOF were 0.149 μM for the inward I NCX and 0.249 μM for outward I NCX, respectively. DOF 0.2 μM significantly enhanced Ca2+ transient and cell shortening in single rat ventricular myocytes driven by field electric stimulation. When the patch clamp system was connected to the ionic imaging system, Ca2+ current (I Ca), Ca2+ transient and cell shortening amplitude in a same cell were recorded synchronously. Application of DOF 0.2 μM had no effect on I Ca, but significantly increased Ca2+ transient and cell shortening. NCX inhibitor KB-R7943 0.6 μM significantly depressed the effects of DOF on Ca2+ transient and cell shortening. We conclude that DOF enhanced contractility of rat ventricular myocytes. The enhancement of NCE may be involved in the positive inotropic action of DOF.