Abstract The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and ...effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.
In February 2019, the Chinese government issued the outline of development planning for Guangdong-Hongkong-Macao Greater Bay Area (GBA), which required all departments in all regions to implement it ...in combination with the actual situation. The implementation of the “one belt and one way” strategy is inseparable from Guangdong with special geographical location and special development orientation. The rapid development of Guangdong relies heavily on the coordinated development of “city cluster + airport group” in GBA. “City cluster + airport group” in GBA will serve as the two centers, and cooperate with each other to carry out the intelligent coordinated development of different industries and the same industries around the two centers.
Promoters are essential tools for basic and translational neuroscience research. An ideal promoter should possess the shortest possible DNA sequence with cell-type selectivity. However, whether ...ultra-compact promoters can offer neuron-specific expression is unclear. Here, we report the development of an extremely short promoter that enables selective gene expression in neurons, but not glial cells, in the brain. The promoter sequence originates from the human CALM1 gene and is only 120 bp in size. The CALM1 promoter (pCALM1) embedded in an adeno-associated virus (AAV) genome directed broad reporter expression in excitatory and inhibitory neurons in mouse and monkey brains. Moreover, pCALM1, when inserted into an all-in-one AAV vector expressing SpCas9 and sgRNA, drives constitutive and conditional in vivo gene editing in neurons and elicits functional alterations. These data demonstrate the ability of pCALM1 to conduct restricted neuronal gene expression, illustrating the feasibility of ultra-miniature promoters for targeting brain-cell subtypes.
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•A 120-bp promoter, pCALM1, drives selective neuronal expression in mouse and macaque brains•pCALM1 efficiently and durably mediates reporter expression after i.c.v./i.v./local delivery•pCALM1 induces strong opsin expression in the mouse motor cortex for behavioral modulations•pCALM1 constitutes an all-in-one SpCas9-expressing AAV for in vivo neuronal genome editing
Wang et al. designed an ultra-compact promoter, pCALM1, which can induce robust and specific gene expression in neurons, but not glia, in rodent and primate brains. pCALM1 efficiently mediates anatomical, functional, and genetic interrogations specifically targeted to neurons.
Background Peripheral T-cell lymphoma (PTCL) is an uncommon disease with poor clinical outcomes. Radiological reports on the survival of patients with PTCL are scarce. The purpose of this study is to ...investigate the prognostic value of CT findings to predict clinical outcomes in fifty-one patients with histologically proven PTCL. Patients and methods The clinical data and CT images of all patients were retrospectively reviewed. CT features including number of involvement sites, lesion size, shape, margin, density, peritumoral invasion, intratumoral necrosis, lymph node involvement, and degree of contrast enhancement were evaluated. Univariate and multiple logistic regression analysis were used to determine the association between the clinical outcome and radiologic factors. Results Multiple site involvement, an ill-defined margin with peritumoral invasion, inhomogeneous density, and intratumoral necrosis were found to be associated with poor outcomes in univariate analysis (P < 0.05). An ill-defined margin with peritumoral invasion, was identified as an independent risk sign by further multivariate logistic regression analysis (P < 0.05). The area under the ROC curve of this CT feature was 0.745 (P < 0.05). Conclusions An ill-defined margin with peritumoral invasion was a valuable prognostic factor to predict the worse clinical outcomes in patients with PTCL.
With the promulgation and implementation of the labor contract law and the law on the promotion of private education, the study of labor relations, especially the discussion on the management of ...labor relations of private colleges and universities, has become a hot topic. As an important part of the main body of higher education in China, private colleges and universities are facing more and more fierce competition, and there are more and more problems facing teachers' labor relations. How to solve the problems in the management of the labor relations of private university teachers and to construct a harmonious and stable labor relationship of private university teachers have become the key to the sustainable development of private colleges and universities. This paper puts forward feasible suggestions from three aspects: macro, meso and micro, so as to help private universities find reasonable solutions to problems.
Modern service industry is one of the industries that widely applies artificial intelligent (AI) in the era of big data. The development of modern service industry plays a very important role in ...industrial transformation. The emergence of AI technology improves the effectiveness of data mining, and more and more scholars suggest a series of optimization methods to lift the prediction ability. In this study, tangent fruit fly optimization algorithm with step adjust (TANSAFOA) is proposed and it is used to optimize multivariate adaptive regression splines (MARS) and back propagation neural network (BPNN) to construct a prediction model of business performance. The result shows TANSAFOA can effectively optimize the prediction model and the BPNN model optimized by TANSAFOA has higher prediction performance than MARS. TANSAFOA BPNN-model is the most appropriate prediction model for modern service industry in China.
Frequent flow of young teachers in independent colleges is a key factor restricting their rapid development. Moreover, the teaching ability of teachers in independent colleges is related to teaching ...quality and personnel training. Scientific and reasonable evaluation index of teaching ability is the key to guarantee teaching quality, and is also an effective way to train and build young teachers. The development of independent colleges is unique, and young teachers also have their own characteristics of the times. This paper will put forward guiding suggestions from the perspective of young teachers' planning and the improvement of young teachers' teaching ability to help the new development of independent colleges.
This article uses a qualitative research methodology to delves into the transformative influence of leadership and trust dynamics on teachers’ innovative work behavior in Chinese higher education. ...Through thematic analysis from 20 educators representing diverse roles, disciplines and institutions from educators, we unveil the essential role of visionary leadership, where leaders inspire a collective sense of purpose by vividly painting the future of education. Concurrently, trust, fostered through transparent communication and shared values, emerges as a cornerstone, creating a safe environment that could inspire educators to experiment with innovative teaching methods. The study also highlights the individual empowerment facilitated by transformative leadership, recognizing and valuing each educator’s unique contributions. While offering valuable insights, this research has limitations, primarily related to the qualitative nature and the specific cultural and institutional context. Suggestions for future research include the use of mixed methods, where both qualitative and quantitative research are important as the use of mixed research methods would be more comprehensive; widening the range of participants and the need to consider the impact of external factors on the educational environment.
Summary
Orthopedia (Otp) is a homeodomain transcription factor that plays an essential role in the development of hypothalamic neurosecretory systems. Loss of Otp results in the failure of ...differentiation of key hypothalamic neuroendocrine cell types, and pups die soon after birth. Although the constitutive knockout Otp mouse model (Otp
KO) has significantly expanded our understanding of Otp's function in vivo, a conditional loss of function Otp allele that enables tissue or cell‐type specific ablation of Otp has not been developed. Here, we used CRISPR/Cas9 gene‐editing technology to generate a conditional Otp knockout mouse line in which exon 2 of the murine Otp gene is flanked by LoxP sites (Otp
f/f). Crossing the Otp
f/f mouse with Agrp‐Ires‐cre mouse, we demonstrate the requirement for Otp in the continuous differentiation of AgRP neurons after cell fate determination. We also show that the residual AgRP neurons in Agrp‐Ires‐cre;Otp
f/f mice project to similar downstream target regions. This newly developed Otp
f/f mouse can be used to explore the functions of Otp with cell‐type or temporal specificity.
Parkinson’s disease (PD) is a debilitating neurodegenerative disorder. Its symptoms are typically treated with levodopa or dopamine receptor agonists, but its action lacks specificity due to the wide ...distribution of dopamine receptors in the central nervous system and periphery. Here, we report the development of a gene therapy strategy to selectively manipulate PD-affected circuitry. Targeting striatal D1 medium spiny neurons (MSNs), whose activity is chronically suppressed in PD, we engineered a therapeutic strategy comprised of a highly efficient retrograde adeno-associated virus (AAV), promoter elements with strong D1-MSN activity, and a chemogenetic effector to enable precise D1-MSN activation after systemic ligand administration. Application of this therapeutic approach rescues locomotion, tremor, and motor skill defects in both mouse and primate models of PD, supporting the feasibility of targeted circuit modulation tools for the treatment of PD in humans.
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•AAV8R12 efficiently transduces striatal D1-, but not D2-, MSNs after nigral delivery•G88P2/3/7 promoters derived from GPR88 gene induce robust gene expression in MSNs•Systemic ligand infusion selectively activates D1-MSNs after nigral AAV8R12/rM3Ds delivery•Single-dose DCZ rescues PD symptoms in primates for at least 24 h without dyskinesia
An AAV-based circuit modulation approach that consists of a designer retrograde AAV capsid, a medium spiny neuron-enriched promoter, and a selected chemogenetic effector specifically modulates direct pathway neurons and rescues parkinsonian symptoms in mouse and macaque Parkinson’s disease models.
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