Brain Science Advances

The Hippo pathway, a highly conserved kinase cascade, regulates cell proliferation, apoptosis, organ size, and tissue homeostasis. Dysregulation of this pathway reportedly plays an important role in the progression of various human cancers. Yes-association protein (YAP), the Hippo pathway’s core effector, is considered a marker for cancer therapy and patient prognosis. In addition, studies have indicated that YAP is involved in promoting anticancer drug resistance. This review summarizes current knowledge on YAP’s role in cancer progression, anticancer drug resistance, and advances in the development of YAP-targeting drugs. A thorough understanding of the complex interactions among molecular, cellular, and environmental factors concerning YAP function in cancer progression may provide new insight into the underlying mechanism of anticancer drug resistance. It might lead to improved prognosis through novel combined therapies.

Alzheimer's disease (AD) so far did not have promising treatment. The accurate and early diagnosis is still the important issue. For these purpose, biomarkers related to diagnosis, clinical course, and other aims have been proposed and reported. Meanwhile, along with the ongoing researches for AD, biomarkers with their own aims are also on the way.

Recent years have witnessed the fascinating development of imaging approaches to studying neural activities; this progress has been based on an influx of ideas and methods from molecular biology and optical engineering. Here we review the design and application of genetically encoded indicators for calcium ions, membrane potential and neurotransmitters. We also summarize common strategies for the design and optimization of genetically encoded neural activity indicators.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. However, it still has no available disease‐modifying therapies. Its pathology cascade begins decades before symptomatic presentation. For these reasons, highly sensitive and highly specific fluid biomarkers should be developed for the early diagnosis of AD. In this study, the well‐established and emerging fluid biomarkers of AD are summarized, and recent advances on their role in early diagnosis and progression monitoring as well as their correlations with AD pathology are highlighted. Future prospects and related research directions are also discussed.

Microvascular decompression (MVD) surgery has been popularized as an etiological treatment around the world for more than half a century. However, as a functional operation in the cerebellopontine angle, this process should be refined to enhance cure and minimize complication. After accomplishing more than 10,000 MVDs, we have learned the following concerning the operative technique: (1) the principle of MVD is to separate the neurovascular confliction, rather than isolate with prostheses; (2) identification of the conflict relies on good exposure; (3) a satisfactory working space can be created by the appropriate positioning, i.e., either a close-to-the-sigmoid craniectomy or caudorostral approach; (4) a sharp dissection of arachnoids leads to a maximal visualization of the entire intracranial course of the nerve root; (5) all vessels contacting the trigeminal nerve root should be cleared off; (6) intraoperative electrophysiological monitoring may predict the prognosis of hemifacial spasm and guide the operation; and (7) the dura must be closed with watertight stitches at the end.

The emerging field of affective computing focuses on enhancing computers’ ability to understand and appropriately respond to people’s affective states in human-computer interactions, and has revealed significant potential for a wide spectrum of applications. Recently, the electroencephalography (EEG) based affective computing has gained increasing interest for its good balance between mechanistic exploration and real-world practical application. The present work reviewed ten theoretical and operational challenges for the existing affective computing researches from an interdisciplinary perspective of information technology, psychology, and neuroscience. On the theoretical side, we suggest that researchers should be well aware of the limitations of the commonly used emotion models, and be cautious about the widely accepted assumptions on EEG-emotion relationships as well as the transferability of findings based on different research paradigms. On the practical side, we propose several operational recommendations for the challenges about data collection, feature extraction, model implementation, online system design, as well as the potential ethical issues. The present review is expected to contribute to an improved understanding of EEG-based affective computing and promote further applications.

Spastic paralysis of the limb mainly results from the central lesion, in which spastic cerebral palsy is the common cause. Due to durative muscle spasm in spastic cerebral palsy, it is often accompanied by the formation of secondary musculoskeletal deformities, resulting in limb motor disability. Based on its pathogenesis, surgical treatment is currently applied: selective posterior rhizotomy (SPR) or orthopedic surgery. The primary purpose of early orthopedic surgery was simply to correct limb deformities, which usually led to the recurrence of deformity as a result of the presence of spasticity. With the application of SPR, high muscle tone was successfully relieved, but limb deformity was still present postoperatively. Therefore, this study aimed to elaborate on the management of orthopedic surgery, common deformities of the lower limb, and orthopedic operative methods; discuss the relationship between SPR and orthopedic procedure for limb deformity; and focus on the indications, timing of intervention, and postoperative outcome of different surgical methods.

Excitatory-inhibitory (E/I) balance is essential for normal neural development, behavior and cognition. E/I imbalance leads to a variety of neurological disorders, such as autism and schizophrenia. NMDA receptors (NMDARs) regulate AMPAR-mediated excitatory and GABA_AR-mediated inhibitory synaptic transmission, suggesting that NMDARs play an important role in the establishment and maintenance of the E/I balance. In this review, we briefly introduced NMDARs, AMPARs and GABA_ARs, summarized the current studies on E/I balance mediated by NMDARs, and discussed the current advances in NMDAR-mediated AMPAR and GABA_AR development. Specifically, we analyzed the role of NMDAR subunits in the establishment and maintenance of E/I balance, which may provide new therapeutic strategies for the recovery of E/I imbalance in neurological disorders.

Large-conductance calcium- and voltage-dependent potassium (BK) channels are ubiquitously expressed in mammalian cells and participate in various physiological and pathological processes such as neurotransmission and cerebral ischemia. BK channels comprise up to four pore-forming α subunits and zero to four accessory subunits. Although microglial BK currents were initially recorded 27 years ago, their roles have long been elusive. Studies have demonstrated that BK channels modulate the activation, phagocytosis, and probably migration of microglia and have associated microglial BK channels with many neurological diseases, including neuropathic pain and stroke. This review summarizes the available information regarding the biophysical, functional, and pathological aspects of microglial BK channels and discusses future directions of research into these channels.

Rhythmicity and oscillations are common features in nature, and can be seen in phenomena such as seasons, breathing, and brain activity. Despite the fact that a single neuron transmits its activity to its neighbor through a transient pulse, rhythmic activity emerges from large population-wide activity in the brain, and such rhythms are strongly coupled with the state and cognitive functions of the brain. However, it is still debated whether the oscillations of brain activity actually carry information. Here, we briefly introduce the biological findings of brain oscillations, and summarize the recent progress in understanding how oscillations mediate brain function. Finally, we examine the possible relationship between brain cognitive function and oscillation, focusing on how oscillation is related to memory, particularly with respect to state-dependent memory formation and memory retrieval under specific brain waves. We propose that oscillatory waves in the neocortex contribute to the synchronization and activation of specific memory trace ensembles in the neocortex by promoting long-range neural communication.

Few studies have investigated the factors associated with the prognosis of children with medulloblastoma. This retrospective observational study evaluated the association of molecular subtype, clinical characteristics, and pathological types with the outcomes of children with medulloblastoma. This study included 40 patients with medulloblastoma who underwent surgical resection at the Affiliated Children's Hospital of Fudan University between January 2004 and June 2014. The primary outcome was overall survival (OS). Risk factors associated with survival, disease progression, and recurrence were analyzed by univariate Cox regression analysis; the identified significant risk factors were further analyzed by Kaplan-Meier survival curves. Immunohistochemistry analysis of Yes-associated protein 1 (YAP1) and GRB2-associated protein 1 (GAB1) was used for medulloblastoma subtype identification; 20% of tumors were the WNT subtype, and 32.5% were the SHH subtype, with the remainder being non-SHH/WNT. Factors associated with OS included M stage, calcification, cerebrospinal fluid fistula, postoperative treatment (radiotherapy, chemotherapy, or both), postoperative Karnofsky Performance Scale score, and molecular subtype (P < 0.044). Patients with the WNT subtype had better survival outcomes (hazard ratio [HR] = 0.16, 95% confidence interval [CI]: 0.05–0.58). Number of symptoms, M stage, and postoperative radiotherapy were associated with disease progression (P ≤ 0.033). The risk of recurrence increased with advanced M stage (HR = 30.71; 95% CI: 3.92—240.44, P = 0.001). Patients receiving both chemotherapy and radiotherapy were less likely to have a recurrence (P = 0.040). Molecular subtyping of medulloblastoma was more predictive of survival than histopathology in patients undergoing adjuvant therapy.