Cholinergic neurons in the pedunculopontine nucleus guide reversal learning by signaling the changing reward contingency.

Cognitive flexibility enables effective switching between mental processes to generate appropriate responses. Cholinergic neurons (CNs) within the pedunculopontine nucleus (PPN) are associated with many functions, but their contribution to cognitive flexibility remains poorly understood. Here we measure PPN cholinergic activities using calcium indicators during the attentional set-shifting task. We find that PPN CNs exhibit increasing activities correlated with rewards during each stage and error trials in reversal stages, indicating sensitivity to rule switching. Inhibition of PPN cholinergic activity selectively impairs reversal learning, which improves with PPN CN activation. Activation of PPN CNs projecting to the substantia nigra pars compacta, mediodorsal thalamus, and parafascicular nucleus in a time-locked manner with reward improves reversal learning. Therefore, PPN CNs may encode not only reward signals but also the information of changing reward contingency that contributes to guiding reversal learning through output projections to multiple nuclei that participate in flexibility.

A review of flexible force sensors for human health monitoring.

BACKGROUND: In recent years, health monitoring systems (HMS) have aroused great interest due to their broad prospects in preventive medicine. As an important component of HMS, flexible force sensors (FFS) with high flexibility and stretch-ability can monitor vital health parameters and detect physical movements. AIM OF REVIEW: In this review, the novel materials, the advanced additive manufacturing technologies, the selective sensing mechanisms and typical applications in both wearable and implantable HMS are discussed. KEY SCIENTIFIC CONCEPTS AND IMPORTANT FINDINGS OF REVIEW: We recognized that the next generation of the FFS will have higher sensitivity, wider linear range as well as better durability, self-power supplied and multifunctional integrated. In conclusion, the FFS will provide powerful socioeconomic benefits and improve people's quality of life in the future.

Anxiolytic Effect of Increased NREM Sleep after Acute Social Defeat Stress in Mice.

Social defeat stress (SDS) plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression. Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS. However, the effect of acute SDS on sleep/wake behavior in mice varies between studies. In addition, whether sleep changes in response to stress contribute to anxiety is not well established. Here, we first investigated the effects of acute SDS on sleep/wake states in the active period in mice. Our results showed that total sleep time (time in rapid eye-movement [REM] and non-REM [NREM] sleep) increased in the active period after acute SDS. NREM sleep increased mainly during the first 3 h after SDS, while REM sleep increased at a later time. Then, we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS. Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state, while in mice with ad libitum sleep the anxiety rapidly faded away. Altogether, our findings suggest an anxiolytic effect of NREM sleep, and indicate a potential therapeutic strategy for anxiety.

Design and biomechanical characteristics of porous meniscal implant structures using triply periodic minimal surfaces.

BACKGROUND: Artificial meniscal implants can be used to replace a severely injured meniscus after meniscectomy and restore the normal functionality of a knee joint. The aim of this paper was to design porous meniscal implants and assess their biomechanical properties. METHODS: Finite element simulations were conducted on eight different cases including intact healthy knees, knee joints with solid meniscal implants, and knee joints with meniscal implants with two types of triply periodic minimal surfaces. Compression stresses, shear stresses, and characteristics of stress concentrated areas were evaluated using an axial compressive load of 1150 N and an anterior load of 350 N. RESULTS: Compared to the solid meniscal implant, the proposed porous meniscal implant produced lower levels of compression and shear stresses on the cartilage, which facilitated the cartilage to retain a semilunar characteristic similar to the natural meniscus. Moreover, both compression and shear stresses on the artificial cartilage were found to be sensitive to the pore properties of the meniscal implant. The meniscal implants with primitive surfaces (porosity: 41%) showed a better performance in disseminating stresses within the knee joint. CONCLUSION: The present commercial meniscal implant has the problem of equivalent biomechanical properties compared to natural menisci. The main advantage of the proposed porous structure is that it can be used to prevent excessive compression and shear stresses on the articular cartilages. This structure has advantages both in terms of mechanics and printability, which can be beneficial for future clinical applications.

Mechanical characterization of 3D printed multi-morphology porous Ti6Al4V scaffolds based on triply periodic minimal surface architectures.

Heterogeneous biomaterials that simultaneously mimic the topological and mechanical properties of nature bone tissues are of great interest in recent years. In this study, multi-morphology porous scaffolds based on the triply periodic minimal surfaces (TPMS) were designed and 3D printed with spatially changing pore patterns. Experiments and numerical analyses were carried out to assess the mechanical properties of the multi-morphology graded porous scaffold. As can be seen from the results, the multi-morphology structure showed a combination of relatively low elastic moduli and high yield strength. This combination allows for simultaneously minimizing the bone damage and increasing the stability of bone-implant interface. Thus the 3D printed multi-morphology porous Ti6AlV scaffold had shown significant promise for orthopedic application.

Effect of disorder on the magnetic properties of a partially filled skutterudite.

The magnetic properties of the partially filled skutterudite Eu(0.5)Co(4)Sb(12) are investigated by a model Hamiltonian, with special emphasis on the effect of ordering and disordering occupancy of the filler atoms Eu on the magnetic properties. The magnetization, magnetic specific heat and entropy are calculated within the mean-field approximation. By introducing the position disorder of the filler atoms, the critical temperature T(C) above which the magnetization disappears is changed. The magnetization curve near T(C) also becomes concave compared to the convex magnetization of the ordered system. The filler disordering also leads to a kink in the isothermal magnetization curve and a valley in the magnetic specific heat near T(C). The effective magnetic field acting on the localized spin of the filler atoms has a competitive effect with the disorder and therefore makes the valley disappear.

[Synthesis and antiinflammation activity of aromatic aminoketone compounds, a new type of PAF-receptor antagonist].

A series of aromatic aminoketones were synthesized by Mannich reaction. Structures of these compounds were confirmed by 1H NMR, MS and HRMS or element analysis. Pharmacological screening showed that most target compounds inhibited the release of beta-glucuronidase in polymorphonuclear leucocytes by PAF (platelet activating factor) and compounds MA12, MA13, MA18, MA21 and MA33 were more active. The study suggests that target compounds are potential PAF receptor antagonists and their anti-inflammatory activities are due to the inhibition of release of lysosomal enzyme.

Pharmacokinetics and tissue distribution of iv injection of polyphase liposome-encapsulated cisplatin (KM-1) in rats.

AIM: The pharmacokinetics and biodistribution of cisplatin encapsulated in polyphase liposome (KM-1) were compared with those of free drug in rats. METHODS: The platinum levels in serum and normal organs, after a single dose of iv injection of free or encapsulated cisplatin to rats, were determined by induced coupled plasma atomic emission spectrometry. RESULTS: Serum platinum concentration-time curve after a single iv dose of KM-1 4.5 mg/kg in rats was fitted with an open three-compartment model. The pharmacokinetic parameters were as follows: Vc=0.10 L/kg, T1/2pai=0.3 h, T1/2alpha=3.5 h, T1/2beta=2.7 h, AUC=265 mg.h.L(-1), and CL(s) =0.02 g.L.h(-1). KM-1 was cleared from the circulation much more slowly than free cisplatin. Liver and spleen had the highest concentration of platinum after KM-1 treatment. CONCLUSION: KM-1 remained in the bloodstream longer than its free drug, and was taken mainly by the reticuloendothelial system.