Neural stem cells and the regulation of adult neurogenesis

Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ), which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL) of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis

Reinforcement learning based optimal decision making towards product lifecycle sustainability

Artificial intelligence (AI) has been widely used in robotics, automation, finance, healthcare, etc. However, using AI for decision-making in sustainable product lifecycle operations is still challenging. One major challenge relates to the scarcity and uncertainties of data across the product lifecycle. This paper aims to develop a method that can adopt the most suitable AI techniques to support decision-making for sustainable operations based on the available lifecycle data. It identifies the key lifecycle stages in which AI, especially reinforcement learning (RL), can support decision-making. Then, a generalised procedure of using RL for decision support is proposed based on available lifecycle data, such as operation and maintenance data. The method has been validated in a case study of an international vehicle manufacturer, combined with modelling and simulation. The case study demonstrates the effectiveness of the method and identifies that RL is the current most appropriate method for maintenance scheduling based on limited available lifecycle data. This paper contributes to knowledge by demonstrating an empirically grounded industrial case using RL to optimise decision-making for improved product lifecycle sustainability by effectively prolonging the product lifetime and reducing environmental impact.Vinnova [2017-01649]

The operation modal analysis of the structure crack fault diagnosis based on pseudo-successive data

In order to monitor the crack propagation of the structure in the working state for a long time, an operation modal analysis method based on pseudo-successive data is proposed. The vibration response signals of the cantilever beam under white noise excitation are collected and the modal parameters are extracted by the time-frequency operation modal analysis method based on the complex Morlet wavelet. In comparison with the experimental modal analysis results of hammering method, it is revealed that the error of the time-frequency operation modal analysis method is less than 10 %. By setting cracks of different lengths on the cantilever beam, the vibration response signals are extracted, and the modal parameters are extracted by the operation modal analysis method separately. By comparing those modal parameters above, it is found that the natural frequencies of the second, the fourth and the sixth orders decrease with the increase of the crack depth, and the changes of natural frequencies show the monotonicity. So, it can be used as an index for quantitative identification of crack damage. The pseudo continuous data monitoring signals of crack propagation can be constructed by means of “first discrete, then continuous”. The modal parameters changes of the whole crack propagation can be observed in one time plane by means of the operation modal analysis method. Therefore, the effective monitoring and diagnosis of the structure can be completed in case of excessive data of long-time vibration monitoring signals

Cortical Neural Stem Cell Lineage Progression Is Regulated by Extrinsic Signaling Molecule Sonic Hedgehog.

Neural stem cells (NSCs) in the prenatal neocortex progressively generate different subtypes of glutamatergic projection neurons. Following that, NSCs have a major switch in their progenitor properties and produce γ-aminobutyric acid (GABAergic) interneurons for the olfactory bulb (OB), cortical oligodendrocytes, and astrocytes. Herein, we provide evidence for the molecular mechanism that underlies this switch in the state of neocortical NSCs. We show that, at around E16.5, mouse neocortical NSCs start to generate GSX2-expressing (GSX2+) intermediate progenitor cells (IPCs). In vivo lineage-tracing study revealed that GSX2+ IPC population gives rise not only to OB interneurons but also to cortical oligodendrocytes and astrocytes, suggesting that they are a tri-potential population. We demonstrated that Sonic hedgehog signaling is both necessary and sufficient for the generation of GSX2+ IPCs by reducing GLI3R protein levels. Using single-cell RNA sequencing, we identify the transcriptional profile of GSX2+ IPCs and the process of the lineage switch of cortical NSCs

Effects of Methotrexate on Plasma Cytokines and Cardiac Remodeling and Function in Postmyocarditis Rats

Excessive immune activation and inflammatory mediators may play a critical role in the pathogenesis of chronic heart failure. Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to investigate the effects of low-dose methotrexate (0.1 mg/kg/d for 30 d) on the plasma level of cytokines and cardiac remodeling and function. Our study showed that levels of tumor necrosis factor-(TNF-)alpha and interleukin-6 (IL-6) are significantly increased in postmyocarditis rats, compared with the control rats. Methotrexate treatment reduced the plasma levels of TNF-alpha and IL-6 and increased IL-10 level, compared to saline treatment. In addition, postmyocarditis rats showed significant cardiac fibrosis characterized by increased myocardial collagen volume fraction, perivascular collagen area, and the ratio of collagen type I to type III, compared with the control rats. However, MTX treatment not only markedly attenuated cardiac fibrosis, diminished the left ventricular end-diastolic dimension, but also increased the left ventricular ejection fraction and fractional shortening. Collectively, these results suggest that low-dose methotrexate has ability to regulate inflammatory responses and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy

Comparison of fungal communities and nonvolatile flavor components in black Huangjiu formed using different inoculation fermentation methods

Black Huangjiu (BH) is a traditional alcoholic beverage in China, which is very popular among people. The different methods (simultaneous inoculation, sequential inoculation), were applied to ferment BH in this study, which were investigated the changes in the composition of fungal communities and non-volatile flavor compounds (nVFCs) by high-throughput sequencing (HTS) and ultraperformance liquid chromatography–tandem mass spectrometer (UPLC MS/MS). The results showed that Rhizopus and Saccharomyces were the predominant fungal genera throughout fermentation, and 471 nVFCs were detected in BH after fermentation. Compared to that observed simultaneous inoculation, Rhizopus increased at the end of sequential fermentation, and the contents of the organic acids and their derivatives increased significantly [variable importance in the projection (VIP) > 1.0, p < 0.05, fold change (FC) > 2], while that of lipids and lipid-like molecules decreased significantly (VIP > 1.0, p < 0.05, FC < 0.5). Through the correlation analysis of 32 nVFCs with significant differences (VIP > 1.0, p < 0.05, FC >32 or < 0.03) and the community, it was found that lipids and lipid-like molecules (12) and organic acids and their derivatives (10) were significantly (p < 0.05) negatively correlated with Saccharomyces, but they were significantly (p < 0.05) positively correlated with Rhizopus. Compared with simultaneous inoculation, BH fermented by sequential inoculation, the taste was stronger, sweeter, mellow, and softer. Our findings provide information on nVFC dynamics and will aid in the selection of beneficial strains to improve BH quality

Disitamab Vedotin (RC48) for HER2-positive advanced breast cancer: a case report and literature review

Background/aimHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with a higher risk of metastasis and poorer overall survival (OS) due to HER2 gene overexpression/amplification. Although anti-HER2 targeted therapy has shown survival benefits in HER2-positive advanced breast cancer (ABC) patients, long-term treatment often leads to drug resistance, complicating further treatment options. RC48, an antibody-drug conjugate (ADC), combines the benefits of antibody targeting with the cytotoxic effects of a small molecule drug.Case reportWe present a case involving a female patient with HER2-positive ABC who developed drug resistance and disease progression following multi-line anti-HER2 targeted therapy. In this instance, RC48 exhibited anti-tumor activity in an ABC patient resistant to HER2-targeted therapy. After eight treatment cycles with 120 mg of RC48, the tumor size decreased and stabilized.ConclusionThis case report underscores the potential clinical value of RC48 as a promising treatment alternative for patients resistant to HER2 targeted therapies

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved