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Brain rhythms provide the timing for recruitment of brain activity required for linking together neuronal ensembles engaged in specific tasks. The γ-oscillations (30 to 120 Hz) orchestrate neuronal circuits underlying cognitive processes and working memory. These oscillations are reduced in numerous neurological and psychiatric disorders, including early cognitive decline in Alzheimers disease (AD). Here, we report on a potent brain-permeable small molecule, DDL-920 that increases γ-oscillations and improves cognition/memory in a mouse model of AD, thus showing promise as a class of therapeutics for AD. We employed anatomical, in vitro and in vivo electrophysiological, and behavioral methods to examine the effects of our lead therapeutic candidate small molecule. As a novel in central nervous system pharmacotherapy, our lead molecule acts as a potent, efficacious, and selective negative allosteric modulator of the γ-aminobutyric acid type A receptors most likely assembled from α1β2δ subunits. These receptors, identified through anatomical and pharmacological means, underlie the tonic inhibition of parvalbumin (PV) expressing interneurons (PV+INs) critically involved in the generation of γ-oscillations. When orally administered twice daily for 2 wk, DDL-920 restored the cognitive/memory impairments of 3- to 4-mo-old AD model mice as measured by their performance in the Barnes maze. Our approach is unique as it is meant to enhance cognitive performance and working memory in a state-dependent manner by engaging and amplifying the brains endogenous γ-oscillations through enhancing the function of PV+INs.

Subcortical white matter stroke (WMS) is a progressive disorder which is demarcated by the formation of small ischemic lesions along white matter tracts in the CNS. As lesions accumulate, patients begin to experience severe motor and cognitive decline. Despite its high rate of incidence in the human population, our understanding of the cause and outcome of WMS is extremely limited. As such, viable therapies for WMS remain to be seen. This study characterizes myelin recovery following stroke and motor learning-based rehabilitation in a mouse model of subcortical WMS. Following WMS, a transient increase in differentiating oligodendrocytes occurs within the peri-infarct in young male adult mice, which is completely abolished in male aged mice. Compound action potential recording demonstrates a decrease in conduction velocity of myelinated axons at the peri-infarct. Animals were then tested on one of three distinct motor learning-based rehabilitation strategies (skilled reach, restricted access to a complex running wheel, and unrestricted access to a complex running wheel) for their capacity to induce repair. These studies determined that unrestricted access to a complex running wheel alone increases the density of differentiating oligodendrocytes in infarcted white matter in young adult male mice, which is abolished in aged male mice. Unrestricted access to a complex running wheel was also able to enhance conduction velocity of myelinated axons at the peri-infarct to a speed comparable to naive controls suggesting functional recovery. However, there was no evidence of motor rehabilitation-induced remyelination or myelin protection.SIGNIFICANCE STATEMENT White matter stroke is a common disease with no medical therapy. A form of motor rehabilitation improves some aspects of white matter repair and recovery.

Decreased expression of the δ subunit of the GABAA receptor (GABAAR) has been found in the dentate gyrus in several animal models of epilepsy and other disorders with increased excitability and is associated with altered modulation of tonic inhibition in dentate granule cells (GCs). In contrast, other GABAAR subunits, including α4 and γ2 subunits, are increased, but the relationship between these changes is unclear. The goals of this study were to determine if viral transfection of δ subunits in dentate GCs could increase δ subunit expression, alter expression of potentially-related GABAAR subunits, and restore more normal network excitability in the dentate gyrus in a mouse model of epilepsy. Pilocarpine-induced seizures were elicited in DOCK10-Cre mice that express Cre selectively in dentate GCs, and two weeks later the mice were injected unilaterally with a Cre-dependent δ-GABAAR viral vector. At 4-6 weeks following transfection, δ subunit immunolabeling was substantially increased in dentate GCs on the transfected side compared to the nontransfected side. Importantly, α4 and γ2 subunit labeling was downregulated on the transfected side. Electrophysiological studies revealed enhanced tonic inhibition, decreased network excitability, and increased neurosteroid sensitivity in slices from the δ subunit-transfected side compared to those from the nontransfected side of the same pilocarpine-treated animal, consistent with the formation of δ subunit-containing GABAARs. No differences were observed between sides of eYFP-transfected animals. These findings are consistent with the idea that altering expression of key subunits, such as the δ subunit, regulates GABAAR subunit assemblies, resulting in substantial effects on network excitability.

Background Self-management meets the long-term rehabilitation needs of stroke patients and their families. However, there is a lack of relevant evidence, and there is no scientific and standardized self-management program in clinical practice. Objective To evaluate and summarize the best evidence of self-management in patients with motor dysfunction after stroke. Methods PubMed, Cochrane Library, Web of Science, Embase, CINAHL, CNKI, Wanfang Data, VIP, Chinese Biomedical Literature Database (CBM), American Heart Association/American Stroke Association (AHA/ASA), World Stroke Organization (WSO), Chinese Stroke Association (CSA), Guidelines International Network (GIN), Scottish Intercollegiate Guidelines Network (SIGN), National Guideline Clearinghouse (NGC), and Yimaitong were searched for relevant research evidence on self-management of patients with motor dysfunction after stroke from inception to July 2022, including guidelines, expert consensuses, systematic reviews, quasi-experimental studies, and randomized controlled studies. Two researchers independently evaluated the quality of the retrieved literature by using the 2017 version of the Appraisal of Guidelines for Research and Evaluation (AGREE Ⅱ) and the 2016 version of the literature evaluation criteria developed by the Joanna Briggs Institute (JBI) Evidence-based Health Care Center, extracted evidence and graded the quality of the evidence to summarize the best evidence of self-management in patients with motor dysfunction after stroke. Results A total of 36 studies were involved, including 9 guidelines, 4 expert consensuses, 5 systematic reviews, 5 quasi-experimental studies, and 13 randomized controlled studies, which were summarized in 6 aspects of organization and management, assessment, exercise instruction, health education, psychological support, monitoring and follow-up, and 34 pieces of best evidence. Conclusion The evidence of self-management in patients with motor dysfunction after stroke summarized in this study contains 6 aspects: organization and management, assessment, exercise instruction, health education, psychological support, monitoring and follow-up. Healthcare workers should select the best evidence based on the individual situation and needs of patients in the context of clinical practice, and provide personalized self-management interventions for patients, so as to improve their motor function and self-management ability, promoting the recovery of disease.

The specification of inhibitory neurons has been described for the mouse and human brain, and many studies have shown that pluripotent stem cells (PSCs) can be used to create interneurons in vitro. It is unclear whether in vitro methods to produce human interneurons generate all the subtypes found in brain, and how similar in vitro and in vivo interneurons are. We applied single-nuclei and single-cell transcriptomics to model interneuron development from human cortex and interneurons derived from PSCs. We provide a direct comparison of various in vitro interneuron derivation methods to determine the homogeneity achieved. We find that PSC-derived interneurons capture stages of development prior to mid-gestation, and represent a minority of potential subtypes found in brain. Comparison with those found in fetal or adult brain highlighted decreased expression of synapse-related genes. These analyses highlight the potential to tailor the method of generation to drive formation of particular subtypes.

While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.

Mossy cells (MCs) of the dentate gyrus (DG) are a major group of excitatory hilar neurons that are important for regulating activity of dentate granule cells. MCs are particularly intriguing because of their extensive longitudinal connections within the DG. It has generally been assumed that MCs in the dorsal and ventral DG have similar patterns of termination in the inner one-third of the dentate molecular layer. Here, we demonstrate that axonal projections of MCs in these two regions are considerably different. MCs in dorsal and ventral regions were labeled selectively with Cre-dependent eYFP or mCherry, using two transgenic mouse lines (including both sexes) that express Cre-recombinase in MCs. At four to six weeks following unilateral labeling of MCs in the ventral DG, a dense band of fibers was present in the inner one-fourth of the molecular layer and extended bilaterally throughout the rostral-caudal extent of the DG, replicating the expected distribution of MC axons. In contrast, following labeling of MCs in the dorsal DG, the projections were more diffusely distributed. At the level of transfection, fibers were present in the inner molecular layer, but they progressively expanded into the middle molecular layer and, most ventrally, formed a distinct band in this region. Optical stimulation of these caudal fibers expressing ChR2 demonstrated robust EPSCs in ipsilateral granule cells and enhanced the effects of perforant path stimulation in the ventral DG. These findings suggest that MCs in the dorsal and ventral DG differ in the distribution of their axonal projections and possibly their function.SIGNIFICANCE STATEMENT Mossy cells (MCs), a major cell type in the hilus of the dentate gyrus (DG), are unique in providing extensive longitudinal and commissural projections throughout the DG. Although it has been assumed that all MCs have similar patterns of termination in the inner molecular layer of the DG, we discovered that the axonal projections of dorsal and ventral MCs differ. While ventral MC projections exhibit the classical pattern, with dense innervation in the inner molecular layer, dorsal MCs have a more diffuse distribution and expand into the middle molecular layer where they overlap and interact with innervation from the perforant path. These distinct locations and patterns of axonal projections suggest that dorsal and ventral MCs may have different functional roles.

More university presses and academic libraries have started to collaborate in the scholarly publishing field, and it becomes important to investigate how this message of collaboration has been delivered to the academic community, since this community includes both creators and users of scholarly works. This study collects 23 news articles on the collaboration between university presses and academic libraries from the formal news sites of the affiliated institutions and then conducts content analysis on these articles, focusing on their content coverage and purposes. These news articles covered topics including the background and benefits of collaboration, how the collaboration worked/would work, and how libraries and presses can contribute to the collaboration. The analysis reveals that these news articles aim not only to inform their readers about the collaboration, but also to provide rationales to the collaboration. The news articles also demonstrate an unbalanced depiction between press and library by focusing more on the press, and this study interprets this phenomenon as a result of two assumptions held by the news articles: the audience's unfamiliarity with the press and more challenging financial viability issues the press encountered.

Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC. [ABSTRACT FROM AUTHOR]