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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.

Background: The increasing prevalence of cognitive impairment poses substantial risks to older adults, particularly those with chronic diseases. While existing studies have examined the connection between the empty nest phenomenon and cognitive function, few have attempted to consider endogeneity issues within this relationship, with limited attention given to older adults with chronic diseases. This study investigates the impact of empty nest status on cognitive function among rural Chinese older adults with chronic diseases and explores the possible mechanisms underlying this effect. Methods: A cross-sectional study involved 365 older adults aged 60 or above with chronic diseases in rural areas of Shaanxi province, northwest China. Cognitive function was measured using the Mini-Mental State Examination. Multiple regression models and the instrumental variable (IV) method were employed to examine the association between empty nest and cognitive function. Results: Among the 365 older adults aged 60 or above with chronic diseases, 43% experienced cognitive impairment. Results from both multiple regression and IV analyses consistently demonstrate a significant association between empty nest status and higher cognitive function scores (β = 1.757, p = 0.007; β = 3.682, p = 0.034, respectively). Mechanism analysis further supports that the positive association may arise from empty nesters receiving more social support from children and friends, and perceiving loneliness experiences as inadequate. Heterogeneity analysis reveals that the association between empty nest status and cognitive function is more pronounced among male adults with chronic diseases. Conclusions: This study challenges the notion that empty nest status is a risk factor for cognitive decline in older adults with chronic diseases in rural China. The positive impact is attributed to the robust social relationships of empty nesters, encompassing sustained support from their social network, and the absence of an increase in loneliness. Therefore, future interventions aimed at improving cognitive function in older adults may benefit from promoting the development of social relationships. [ABSTRACT FROM AUTHOR]

Li‐rich cathode materials (LRMs) are regarded as the key cathode candidates for next‐generation lithium‐ion batteries(LIBs) because of their high specific capacity and environmental friendliness. However, LRMs encounter poor cyclability and low initial coulombic efficiency (ICE) hindering their practical application. Herein, a general near‐surface in situ reconstruction strategy is proposed of constructing the Li/O dual vacancies and spinel‐carbon dual coating layers on the surface of LRMs concurrently to improve Li+ storage performance. The as‐prepared LRMs exhibit a greatly strengthened specific capacity of 283 mAh g−1 with an enhanced ICE of 94% and long‐term cyclability of 91% retention after 200 cycles compared with the pristine LRMs (212 mAh g−1 with an ICE of 65%, 76% retention after 200 cycles). Furthermore, it is theoretically revealed that O vacancies (Ov) prefer to occur at the interface of the C2/m and R3¯$\bar{3}$m phases to mitigate lattice stress, rather the O sites in individual C2/m or R3¯$\bar{3}$m phase with more coordinated atoms. Besides, Li ions exhibit lower migration energy from C2/m phase to R3¯$\bar{3}$m phase with the Ov located at the lattice interface. Therefore, this strategy opens a new avenue in the design perspective of the LRMs' near‐surface for high‐energy‐density LIBs. [ABSTRACT FROM AUTHOR]

Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions. Microglia undergo rapid phenotype changes in response to tissue disturbances but the impact of these changes on neuronal networks is unclear. Here, the authors show that microglia contribute to neuronal synchrony in acute brain slices, while their marked phenotypic transformation is influenced by injury-related focal ATP events. [ABSTRACT FROM AUTHOR]

Objectives: In middle-income countries, poor physician-patient communication remains a recognized barrier to enhancing healthcare quality and patient satisfaction. This study investigates the influence of provider-patient communication skills on healthcare quality and patient satisfaction in the rural primary healthcare setting in China. Methods: Data were collected from 504 interactions across 348 rural primary healthcare facilities spanning 21 counties in three provinces. Using the Standardized Patient method, this study measured physician-patient communication behaviors, healthcare quality, and patient satisfaction. Communication skills were assessed using the SEGUE questionnaire framework. Multivariate linear regression models and multivariate logistic regression models, accounting for fixed effects, were employed to evaluate the impact of physicians' communication skills on healthcare quality and patient satisfaction. Results: The findings indicated generally low provider-patient communication skills, with an average total score of 12.2 ± 2.8 (out of 24). Multivariate regression models, which accounted for physicians' knowledge and other factors, demonstrated positive associations between physicians' communication skills and healthcare quality, as well as patient satisfaction (P < 0.05). Heterogeneity analysis revealed stronger correlations among primary physicians with lower levels of clinical knowledge or more frequent training. Conclusion: This study emphasizes the importance of prioritizing provider-patient communication skills to enhance healthcare quality and patient satisfaction in rural Chinese primary care settings. It recommends that the Chinese government prioritize the enhancement of provider-patient communication skills to improve healthcare quality and patient satisfaction. [ABSTRACT FROM AUTHOR]

To investigate the influence mechanism of the light-off characteristics and secondary pollutants (N2O and NH3) of the Pd/Rh catalytic converter for natural gas engines, a global model of the catalytic converter and a more comprehensive catalytic reaction mechanism were first established. Further, the model and the catalytic reaction mechanism were validated by using experimental data. Then, the effects of exhaust temperature and exhaust composition (H2O, O2, and H2 concentrations) on the catalytic converters were investigated. The results showed that a higher temperature reduced the light-off time t50 of NO and CO. The production of N2O decreased to 0 at high temperatures due to the reduction reactions of R14 (N2O+H2 = H2O+N2) and R16 (N2O+CO = CO2 + N2). NH3 would form at the temperature above 825 K, and the required H2 originated from SR and WGS reactions. Increasing the H2 concentration promoted the conversion of NO and CO. When the temperature exceeds 600 K, increasing the H2 concentration decreases the production of N2O. H2O has the opposite effect on the production of N2O and NH3 at high temperatures. Increasing the content of H2O increased the conversion of NO and inhibited the conversion of CO. O2 concentration at 4000 × 10−6 is beneficial to reduce secondary pollutants of N2O and NH3. At the condition of 730–820 K and 4000 × 10−6 O2, the productions of N2O and NH3 were reduced to 0. This study contributes to the efficient application of Pd/Rh catalytic converters and further enhances the emission reduction of natural gas engines. [ABSTRACT FROM AUTHOR]