Search

Background & Aims: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B‐related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction‐associated steatotic liver disease (MASLD; formerly NAFLD)‐related fibrosis diagnosis and establish a machine‐learning (ML) model to improve the diagnostic performance. Methods: A total of 946 biopsy‐proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). Results: The AUROCs of aMAP versus fibrosis‐4 index (FIB‐4) and aspartate aminotransferase‐platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut‐off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB‐4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM‐plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM‐plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM‐plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). Conclusions: The aMAP score is capable of diagnosing MASLD‐related fibrosis. The LSM‐plus model could accurately identify MASLD‐related cirrhosis and advanced fibrosis. [ABSTRACT FROM AUTHOR]

Corticotropin‐releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus‐based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain. [ABSTRACT FROM AUTHOR]

The magnetized solar wind drives a current system around Mars that maintains its induced magnetosphere. The solar wind also transfers its energy to the atmospheric ions, causing continuous atmospheric erosion, which has a profound impact on the planet's evolution history. Here, we use Amitis, a Graphics Processing Unit (GPU)-based hybrid plasma model to first reproduce the global pattern of the net electric current and ion currents under an interplanetary magnetic field perpendicular to the solar wind flow direction. The resultant current distribution matches the observations and reveals more details. Using the electric field distribution characterized earlier with the same model, we calculate for the first time the spatial distribution of energy transfer rate to the plasmas in general and to different ion species at Mars. We find out that (1) the solar wind kinetic energy is the dominant energy source that drives Martian induced magnetosphere, (2) the energy flux of the shocked solar wind flows from the magnetic equatorial plane towards the plasma sheet in the induced magnetotail, (3) both the bow shock and the induced magnetospheric boundary are dynamos where plasma energy is transferred to the electromagnetic field, and (4) the planetary ions act as loads and gain energy from the electromagnetic field. The most intense load region is the planetary ion plume. The general pattern of the energy transfer rate revealed in this study is common for induced magnetospheres. Its variabilities with the upstream conditions can provide physical insight into the observed ion escape variabilities. [ABSTRACT FROM AUTHOR]

Polymethacrylimide foams were prepared by free radical bulk polymerization with butyl methacrylate (BMA), acrylamide (AM) as the reactive monomer, acrylic acid (AA) as the third monomer and crosslinker at different heat treatment time. The structure and properties were characterized by FTIR, SEM, TGA and DSC. The results show that with the increase of heat treatment time of BMA/AM/AA copolymer, the rearrangement reaction between molecular chains produces a six-membered imide ring. After cross-linking and solidification, PMI foam is obtained. The characteristic absorption peaks are in good agreement with the literature values. After heat treatment for 5 h, a dense closed cell foam with a pore diameter of 100-200 μm is obtained, which has good mechanical properties, compressive strength of 8.160 MPa and tensile strength of 12.95 MPa. The glass transition temperature (Tg) of the foam is 255℃, the thermal decomposition temperature Td10 is as high as 280℃ when the thermal mass loss is 10%, and the foam still retains more than 80% at 345℃, and the thermal conductivity is 0.05424 W/(m·K). It is indicated that the foam with excellent high temperature resistance and thermal insulation properties is obtained after heat treatment of the copolymer for 5 h.

Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF₁), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF₁ knock-out (CRF₁-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF₁ in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF₁ deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF₁-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF₁ signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity.

Chronic stress evokes profound structural and molecular changes in the hippocampus, which may underlie spatial memory deficits. Corticotropin-releasing hormone (CRH) and CRH receptor 1 (CRHR1) mediate some of the rapid effects of stress on dendritic spine morphology and modulate learning and memory, thus providing a potential molecular basis for impaired synaptic plasticity and spatial memory by repeated stress exposure. Using adult male mice with CRHR1 conditionally inactivated in the forebrain regions, we investigated the role of CRH-CRHR1 signaling in the effects of chronic social defeat stress on spatial memory, the dendritic morphology of hippocampal CA3 pyramidal neurons, and the hippocampal expression of nectin-3, a synaptic cell adhesion molecule important in synaptic remodeling. In chronically stressed wild-type mice, spatial memory was disrupted, and the complexity of apical dendrites of CA3 neurons reduced. In contrast, stressed mice with forebrain CRHR1 deficiency exhibited normal dendritic morphology of CA3 neurons and mild impairments in spatial memory. Additionally, we showed that the expression of nectin-3 in the CA3 area was regulated by chronic stress in a CRHR1-dependent fashion and associated with spatial memory and dendritic complexity. Moreover, forebrain CRHR1 deficiency prevented the down-regulation of hippocampal glucocorticoid receptor expression by chronic stress but induced increased body weight gain during persistent stress exposure. These findings underscore the important role of forebrain CRH-CRHR1 signaling in modulating chronic stress-induced cognitive, structural and molecular adaptations, with implications for stress-related psychiatric disorders.