Cortical hem signaling center: functions, development, and potential implications for evolution and brain disorders

Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical neuroepithelium.One such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in mice.The cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)proteins.The cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).

Peking University Health Science Center Model of Clinica Pharmacy Education and Clinical Pharmacist Services

In the 1950s, clinical pharmacy emerged in the United States and gradually developed into an indispensable component of the clinical services system, The American College of Clinical Pharmacy defines clinical pharmacy as a pharmaceutical field that focuses on the science and practice of rational drug use.

Strategic Study on the Development of Space Science in China and Proposals for Future Missions

Since 2011,the Chinese Academy of Sciences(CAS)has implemented the Strategic Priority Program on Space Science(SPP).A series of scientific satellites have been developed and launched,such as Dark Matter Particle Explorer(DAMPE),Quantum Experiments at Space Scale(QUESS),Advanced Space-based Solar Observatory(ASO-S),Einstein Probe(EP),and significant scientific outcomes have been achieved.In order to plan the future space science missions in China,CAS has organized the Chinese space science community to conduct medium and long-term development strategy studies,and summarized the major scientific frontiers of space science as“One Black,Two Dark,Three Origins and Five Characterizations”.Five main scientific themes have been identified for China’s future breakthroughs,including the Extreme Universe,Space-Time Ripples,the Panoramic View of the Sun and Earth,the Habitable Planets,and Biological&Physical Science in Space.Space science satellite missions to be implemented before 2030 are proposed accordingly.

Features of gastric cancer by anatomic subsite in northern China: A multi-center Health Science Report database study

BACKGROUND The features of gastric cancer based on the anatomic site remain unknown in northern China patients.AIM To analyze gastric cancer features and associated trends based on the anatomical site in northern China patients.METHODS This cross-sectional study used incident gastric cancer case data from 10 Peking University-affiliated hospitals(2014 to 2018).The clinical and prevailing local features were analyzed.RESULTS A total of 10709 patients were enrolled,including antral(42.97%),cardia(34.30%),and stomach body(18.41%)gastric cancer cases.Cancer in the cardia had the highest male:female ratio,proportion of elderly patients,and patients with complications,including hypertension,diabetes,cerebrovascular,and coronary diseases(P<0.001).gastric cancer involving the antrum showed the lowest proportion of patients from rural areas and accounted for the highest hospitalization rate and cost(each P<0.001).The proportion of patients with cancer involving the cardia increased with an increase in the number of gastroesophageal reflux disease cases during the same period(P<0.001).Multivariate analysis revealed that tumor location in the cardia increased the risk of inhospital mortality(P=0.046).Anatomical subsite was not linked to postoperative complications.CONCLUSION The features of gastric cancer based on the anatomical site differ between northern China and other regions,both globally and within the country.Social factors may account for these differences and should affect policy-making and clinical practice.

Cryogenic transmission electron microscopy on beam-sensitive materials and quantum science

Transmission electron microscopy(TEM)offers unparalleled atomic-resolution imaging of complex materials and heterogeneous structures.However,high-energy imaging electrons can induce structural damage,posing a challenge for electron-beam-sensitive materials.Cryogenic TEM(Cryo-TEM)has revolutionized structural biology,enabling the visualization of biomolecules in their near-native states at unprecedented detail.The low electron dose imaging and stable cryogenic environment in Cryo-TEM are now being harnessed for the investigation of electron-beam-sensitive materials and low-temperature quantum phenomena.Here,we present a systematic review of the interaction mechanisms between imaging electrons and atomic structures,illustrating the electron beam-induced damage and the mitigating role of Cryo-TEM.This review then explores the advancements in low-dose Cryo-TEM imaging for elucidating the structures of organic-based materials.Furthermore,we showcase the application of Cryo-TEM in the study of strongly correlated quantum materials,including the detection of charge order and novel topological spin textures.Finally,we discuss the future prospects of Cryo-TEM,emphasizing its transformative potential in unraveling the complexities of materials and phenomena across diverse scientific disciplines.

Introducing hydroxyl groups to tailor the d-band center of Ir atom through side anchoring for boosted ORR and HER

Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of hydrogen-substituted graphdiyne(HsGDY),and coordinated with OH as an Ir atomic catalyst(Ir_(1)-N-HsGDY).The electron structures,especially the d-band center of Ir atom,are optimized by these specific coordination atoms.Thus,the as-synthesized Ir_(1)-N-HsGDY exhibits excellent electrocatalytic performances for oxygen reduction and hydrogen evolution reactions in both acidic and alkaline media.Benefiting from the unique structure of HsGDY,IrN_(2)(OH)_(3) has been developed and demonstrated to act as the active site in these electrochemical reactions.All those indicate the fresh role of the sp-N in graphdiyne in producing a new anchor way and contributing to promote the electrocatalytic activity,showing a new strategy to design novel electrochemical catalysts.

Clinical characteristics and prognosis of takotsubo syndrome patients in single center

Takotsubo syndrome(TTS)is a clinical syndr-ome that frequently occurs in postmenopausal women,mostly induced by stress factors.It is characterized by chest pain,ST-segment elevation,and/or T-wave changes in electrocardiogram,along with my-ocardial troponin elevation.[1]TTS can be easily misdia-gnosed as myocardial infarction,and improper treatme-nt may lead to serious consequences.There are few re-ports and research on this disease.[2]

Maximizing Resource Efficiency in Cloud Data Centers through Knowledge-Based Flower Pollination Algorithm (KB-FPA)

Cloud computing is a dynamic and rapidly evolving field,where the demand for resources fluctuates continuously.This paper delves into the imperative need for adaptability in the allocation of resources to applications and services within cloud computing environments.The motivation stems from the pressing issue of accommodating fluctuating levels of user demand efficiently.By adhering to the proposed resource allocation method,we aim to achieve a substantial reduction in energy consumption.This reduction hinges on the precise and efficient allocation of resources to the tasks that require those most,aligning with the broader goal of sustainable and eco-friendly cloud computing systems.To enhance the resource allocation process,we introduce a novel knowledge-based optimization algorithm.In this study,we rigorously evaluate its efficacy by comparing it to existing algorithms,including the Flower Pollination Algorithm(FPA),Spark Lion Whale Optimization(SLWO),and Firefly Algo-rithm.Our findings reveal that our proposed algorithm,Knowledge Based Flower Pollination Algorithm(KB-FPA),consistently outperforms these conventional methods in both resource allocation efficiency and energy consumption reduction.This paper underscores the profound significance of resource allocation in the realm of cloud computing.By addressing the critical issue of adaptability and energy efficiency,it lays the groundwork for a more sustainable future in cloud computing systems.Our contribution to the field lies in the introduction of a new resource allocation strategy,offering the potential for significantly improved efficiency and sustainability within cloud computing infrastructures.

A Systematic Literature Review on Task Allocation and Performance Management Techniques in Cloud Data Center

As cloud computing usage grows,cloud data centers play an increasingly important role.To maximize resource utilization,ensure service quality,and enhance system performance,it is crucial to allocate tasks and manage performance effectively.The purpose of this study is to provide an extensive analysis of task allocation and performance management techniques employed in cloud data centers.The aim is to systematically categorize and organize previous research by identifying the cloud computing methodologies,categories,and gaps.A literature review was conducted,which included the analysis of 463 task allocations and 480 performance management papers.The review revealed three task allocation research topics and seven performance management methods.Task allocation research areas are resource allocation,load-Balancing,and scheduling.Performance management includes monitoring and control,power and energy management,resource utilization optimization,quality of service management,fault management,virtual machine management,and network management.The study proposes new techniques to enhance cloud computing work allocation and performance management.Short-comings in each approach can guide future research.The research’s findings on cloud data center task allocation and performance management can assist academics,practitioners,and cloud service providers in optimizing their systems for dependability,cost-effectiveness,and scalability.Innovative methodologies can steer future research to fill gaps in the literature.

Ground-based and additional science support for SMILE

The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere.Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission.Here,we describe current community efforts to prepare for SMILE,and the benefits and context various experiments that have explicitly expressed support for SMILE can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the Ground-based and Additional Science Working Group,is facilitating these efforts.Preparations include constructing an online SMILE Data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft conjunctions.We anticipate growing interest and community engagement with the SMILE mission,and we welcome novel ideas and insights from the solar-terrestrial community.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

Emerging insights into the function of very long chain fatty acids at cerebellar synapses

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

Role of peripheral amyloid-β aggregates in Alzheimer’s disease: mechanistic, diagnostic, and therapeutic implications

Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.

Misfolded amyloid-beta conformational variants(strains)as drivers of Alzheimer's disease neuropathology

Pathological and clinical variability in Alzheimer's disease(AD):AD is clinically cha racterized by progressive memory loss and cognitive impairment.From a pathological point of view,the main features of AD are the deposition of amyloid plaques(composed of amyloid-beta,Aβ)and neurofibrillary tangles containing hyperphosphorylated Tau in the brain,accompanied by neu ronal and synaptic loss,neuroinflammation and brain atrophy(Jellinger,2022).Regardless of these common traits,growing evidence shows increased heterogen eity in the brain of AD patients considering both clinical manifestations and pathological features.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

The low-latitude sodium layer:comparative data from lidar observations at Hainan,China and São Paulo,Brazil

Physical and chemical processes observed in the mesosphere and thermosphere above the Earth’s low latitudes are complex and highly interrelated to activity in the low-latitude ionosphere.Metallic sodium detected by lidar can yield clues to dynamic and chemical processes in these spatial layers above the Earth’s atmosphere.This paper is based on sodium layer data collected at two low-latitude stations,one in the northern hemisphere and one in the southern.The low-latitude sodium layer exhibits conspicuous seasonal variations in shape,density,and altitude;these variations are similar between Earth’s hemispheres:sodium layer density at both stations reaches its seasonal maximum in autumn and minimum in summer.However,maximal Na density over Brazil is greater than that over Hainan.Nocturnal variations of Na density above the two low-latitude stations are also similar;at both,maxima are observed before sunrise.Some variations of the Na layer over Brazil that differ from those observed in the northern hemisphere may be related to the South Atlantic Magnetic Anomaly(SAMA)or fountain effect.We suggest that low-latitude Na layer data may provide useful additional evidence that could significantly improve the low-latitude part of the WACCM-Na model.

High Fe‑Loading Single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.