Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during VisualDiscrimination

Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition

Early Development of Network Oscillations in the Ferret Visual Cortex

Abstract Although oscillations during development have been characterized in a wide range of neural systems, little is known about the interaction between these network oscillations and neuronal spiking, and the interactions among different oscillation frequencies. Here we recorded the spontaneous and visual-elicited local field potential (LFP) and multi-unit activity (MUA) in the visual cortex of freely-moving juvenile ferrets before and after eye-opening. We found that both the spontaneous and visually-elicited LFP power was increased after eye-opening, especially in higher frequency bands (>30 Hz). Spike LFP phase coupling was decreased for lower frequency bands (theta and alpha) but slightly increased for higher frequencies (high-gamma band). A similar shift towards faster frequencies also occurred for phase-amplitude coupling; with maturation, the coupling of the theta/alpha/beta band amplitude to the delta phase was decreased and the high-gamma amplitude coupling to theta/alpha phase was increased. This shift towards higher frequencies was also reflected in the visual responses; the LFP oscillation became more entrained by visual stimulation with higher frequencies (>10 Hz). Taken together, these results suggest gamma oscillation as a signature of the maturation of cortical circuitry

A Comprehensive Correlation Study of Structured Soils in Coastal Area of South China about Structural Characteristics

Granite residual soil is a common engineering material, and its mechanical properties are of great importance to engineering safety. This kind of soil presents obvious structural characteristics, and many researchers have emphasized the significance of its structural features. According to previous experiments, from a macroscopic perspective, many researchers have investigated the structural relationship between undisturbed and remolded soils, but few studies have considered it in the mesoscopic aspect. Adopting DEM (a mesomechanical simulation method), we can study how the structure affects the mechanical process between undisturbed and remolded soil. Therefore, this paper combines DEM with laboratory tests to study the structural characteristic correlation between undisturbed and remolded soil. The results indicate that a weak cohesion effect exists in undisturbed soil, and the damage of weak cohesion elements accompanies the failure process. Weak cohesion elements in undisturbed soil cause inhomogeneities in deformation, stress state, and damage accumulation, which ultimately causes differences in strength curves. This paper explains the mechanism of the structural effect on mechanical evolution from a mesomechanical perspective. The DEM simulation method proposed in this paper can be applied to structured soils and better guide engineering practice

3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway

3,4′,5-trimethoxy-trans-stilbene (TMS) is a methoxylated derivative of resveratrol. Previous studies showed the vaso-protective effects of resveratrol; nevertheless, research on this derivative is scarce. The current study aimed to explore whether TMS can alleviate endothelial dysfunction in diabetic and obese mice, along with the underlying mechanisms. Thoracic aortas isolated from male C57BL/6J mice and primary cultures of rat aortic endothelial cells were treated with high glucose with or without TMS. High glucose exposure impaired acetylcholine-induced endothelium-dependent relaxations, down-regulated NO bioavailability and the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1)/endothelial nitric oxide synthase (eNOS) pathway, increased endoplasmic reticulum (ER) stress and oxidative stress, which were reversed by TMS treatment. Moreover, the protective effects of TMS were abolished by Compound C (AMPK inhibitor), and EX527 (SIRT1 inhibitor). The mice were fed with high-fat diet (60% kcal% fat) for 14 weeks to establish a diabetic and obese model, and were orally administered TMS (10 mg/kg/day) in the last 4 weeks. Chronic TMS treatment alleviated endothelial dysfunction via enhancing the AMPK/SIRT1/eNOS pathway and attenuated oxidative stress and ER stress in aortas of diet-induced obese mice. In summary, our study reveals the potent vaso-protective effect of TMS and its therapeutic potential against endothelial dysfunction in metabolic disorders

A framework for electric vehicle power supply chain development

One anticipated pathway in society's decarbonization is the electrification of the transportation sector. From a power system perspective, transitioning to electric vehicles (EVs) presages many impacts, both positive and negative. This study utilizes the theoretical framework of business model theory and a review of the existing literature to portray a rational development path for the electric vehicle power supply chain (EVPSC). Three phases of development were identified in which EVs transition from the present day's low utilization, to rapid development, to a mature technology dominating the transportation sector. Within these phases, the business content, business structure, and corresponding coordination modes were analyzed and discussed. The three phases of development are shown to dynamically interact, between development phases and the business models, providing insight into the content of the EVPSC. Such insight is necessary for developing coherent policies and institutional supports to foster efficient development of the EVPSC. This study provides a new perspective about EVPSC development, answers the core question on how to realize the coordinated development between EVs and the electric power system chain (EPSC) based on the model of EVPSC, and provides recommendations on the establishment of business models for the future EVPSC

Citri Reticulatae Pericarpium (Chenpi) Protects against Endothelial Dysfunction and Vascular Inflammation in Diabetic Rats

Dried tangerine peel (Citri reticulatae Pericarpium, CRP; Chenpi in Chinese) possesses medicine and food homology with hypolipidemic, anti-inflammatory and antioxidant activities. This study aimed to explore the protective effect of CRP extract on endothelial function and inflammation in type 2 diabetic rats and the related mechanisms. Type 2 diabetes mellitus was induced by high-fat diet (HFD)/streptozotocin (STZ) in male Sprague Dawley rats, and CRP extract was orally administered at 400 mg/kg/day for 4 weeks. Rat and mouse aortas were treated with high glucose and CRP extract ex vivo. The data showed that the ethanolic extract of CRP normalized blood pressure and the plasma lipid profile as well as the plasma levels of liver enzymes in diabetic rats. Impaired endothelium-dependent relaxations in aortas, carotid arteries and renal arteries were improved. CRP extract suppressed vascular inflammatory markers and induced AMPK activation in aortas of diabetic rats. Exposure to high glucose impaired vasodilation in aortas of rats and mice, and this impairment was prevented by co-incubation with CRP extract. In conclusion, our findings suggest that CRP extract protects endothelial function by inhibiting the vascular inflammatory state on activation of AMPK in diabetic rats

Development of FRET and Stress Granule Dual-Based System to Screen for Viral 3C Protease Inhibitors

3C proteases (3Cpros) of picornaviruses and 3C-like proteases (3CLpros) of coronaviruses and caliciviruses represent a group of structurally and functionally related viral proteases that play pleiotropic roles in supporting the viral life cycle and subverting host antiviral responses. The design and screening for 3C/3CLpro inhibitors may contribute to the development broad-spectrum antiviral therapeutics against viral diseases related to these three families. However, current screening strategies cannot simultaneously assess a compound’s cytotoxicity and its impact on enzymatic activity and protease-mediated physiological processes. The viral induction of stress granules (SGs) in host cells acts as an important antiviral stress response by blocking viral translation and stimulating the host immune response. Most of these viruses have evolved 3C/3CLpro-mediated cleavage of SG core protein G3BP1 to counteract SG formation and disrupt the host defense. Yet, there are no SG-based strategies screening for 3C/3CLpro inhibitors. Here, we developed a fluorescence resonance energy transfer (FRET) and SG dual-based system to screen for 3C/3CLpro inhibitors in living cells. We took advantage of FRET to evaluate the protease activity of poliovirus (PV) 3Cpro and live-monitor cellular SG dynamics to cross-verify its effect on the host antiviral response. Our drug screen uncovered a novel role of Telaprevir and Trifluridine as inhibitors of PV 3Cpro. Moreover, Telaprevir and Trifluridine also modulated 3Cpro-mediated physiological processes, including the cleavage of host proteins, inhibition of the innate immune response, and consequent facilitation of viral replication. Taken together, the FRET and SG dual-based system exhibits a promising potential in the screening for inhibitors of viral proteases that cleave G3BP1

Theta Oscillations Organize Spiking Activity in Higher-Order Visual Thalamus during Sustained Attention

Higher-order visual thalamus plays a fundamental but poorly understood role in attention-demanding tasks. To investigate how neuronal dynamics in higher-order visual thalamus are modulated by sustained attention, we performed multichannel electrophysiological recordings in the lateral posterior-pulvinar complex (LP/pulvinar) in the ferret (Mustela putorius furo). We recorded single unit activity and local field potential (LFP) during the performance of the five-choice serial reaction time task (5-CSRTT), which is used in both humans and animals as an assay of sustained attention. We found that half of the units exhibited an increasing firing rate during the delay period before stimulus onset (attention-modulated units). In contrast, the non-attention-modulated units responded to the stimulus, but not during the delay period. Spike-field coherence (SFC) of only the attention-modulated neurons significantly increased from the start of the delay period until screen touch, predominantly in the θ frequency band. In addition, θ power and θ/γ phase amplitude coupling (PAC) were elevated throughout the delay period. Our findings suggest that the θ oscillation plays a central role in orchestrating thalamic signaling during sustained attention

Serum lipid profiling of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma by ultra fast LC/IT-TOF MS

In this study, an ultra fast LC/IT-TOF MS (UFLC/IT-TOF MS)-based serum lipidomics method was employed to characterize the serum lipid profile of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC). After data collection and processing, 96 lipids including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, triacylglycerides, and cholesterol esters were identified and used for subsequent data analysis. Partial least squares-discriminant analysis revealed that patients with liver diseases had distinctly different serum lipid profile from that of healthy controls; while cirrhosis and HCC patients had a similar serum lipid profile, but different from that of hepatitis patients. The ANOVA analysis found 75 of the 96 identified lipids to be abnormally regulated, among which most of these lipids were downregulated in cirrhosis and HCC patients compared with those of healthy controls and hepatitis patients, while hepatitis patients induced several lipids downregulated and others upregulated compared with those of healthy controls, indicating the aberrant lipid metabolism in patients with liver diseases. This work demonstrated the utility of UFLC/IT-TOF MS-based serum lipidomics as a powerful tool to investigate the lipid metabolism of liver diseases