Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Mammalian hibernation:a unique model for medical research

Hibernation is an adaptive behavior for some small animals to survive cold winter.Hibernating mammals usually down-regulate their body temperature from~37℃to only a few degrees.During the evolution,mammalian hibernators have inherited unique strategies to survive extreme conditions that may lead to disease or death in humans and other non-hibernators.Hibernating mammals can not only tolerant deep hypothermia,hypoxia and anoxia,but also protect them against osteoporosis,muscle atrophy,heart arrhythmia and ischemia-reperfusion injury.Finding the molecular and regulatory mechanisms underlying these adaptations will provide novel ideas for treating related human diseases.

Reconfigurable Mott electronics for homogeneous neuromorphic platform

To simplify the fabrication process and increase the versatility of neuromorphic systems,the reconfiguration concept has attracted much attention.Here,we developed a novel electrochemical VO_(2)(EC-VO_(2))device,which can be reconfigured as synapses or LIF neurons.The ionic dynamic doping contributed to the resistance changes of VO_(2),which enables the reversible modulation of device states.The analog resistance switching and tunable LIF functions were both measured based on the same device to demonstrate the capacity of reconfiguration.Based on the reconfigurable EC-VO_(2),the simulated spiking neural network model exhibited excellent performances by using low-precision weights and tunable output neurons,whose final accuracy reached 91.92%.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

A Wnt10a-Notch signaling axis controls Hertwig’s epithelial root sheath cell behaviors during root furcation patterning

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig’s epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a^(fl/fl)mice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a^(fl/fl)mice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10a^(fl/fl)molars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

All-fiber-transmission photometry for simultaneous optogenetic stimulation and multi-color neuronal activity recording

Manipulating and real-time monitoring of neuronal activities with cell-type specificity and precise spatiotemporal resolution during animal behavior are fundamental technologies for exploring the functional connectivity, information transmission, and physiological functions of neural circuits in vivo. However, current techniques for optogenetic stimulation and neuronal activity recording mostly operate independently. Here, we report an all-fiber-transmission photometry system for simultaneous optogenetic manipulation and multi-color recording of neuronal activities and the neurotransmitter release in a freely moving animal. We have designed and manufactured a wavelength-independent multi-branch fiber bundle to enable simultaneous optogenetic manipulation and multi-color recording at different wavelengths. Further, we combine a laser of narrow linewidth with the lock-in amplification method to suppress the optogenetic stimulation-induced artifacts and channel crosstalk. We show that the collection efficiency of our system outperforms a traditional epi-fluorescence system. Further, we demonstrate successful recording of dynamic dopamine(DA) responses to unexpected rewards in the nucleus accumbens(NAc) in a freely moving mouse. We also show simultaneous dual-color recording of neuronal Ca2+ signals and DA dynamics in the NAc upon delivering an unexpected reward and the simultaneous optogenetic activating at dopaminergic terminals in the same location. Thus, our multi-function fiber photometry system provides a compatible, efficient, and flexible solution for neuroscientists to study neural circuits and neurological diseases.

Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases:executive summary and 2023 update

Background China is one of the countries with the highest burden of stroke.Implementing multidimensional management guidelines will help clinicians practise evidence-based care,improve patient outcomes and alleviate societal burdens.This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases.Methods We conducted a comprehensive search on MEDLINE(via PubMed)up to 31 August 2023.The writing team established the recommendations through multiple rounds of online and offline discussions.Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association(CSA).The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee.Results This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care:emergency assessment and diagnosis of ischaemic cerebrovascular disease,acute-phase reperfusion therapy,evaluation of underlying mechanisms,antithrombotic therapy,prevention and treatment of complications,and risk factor management.Conclusions This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen.Tirofiban,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic stroke.However,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear.Aim To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination.Methods Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in China.Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90.The primary endpoint is a new stroke or END within 90 days.The primary safety endpoint is severe or moderate bleeding within 90 days.Discussion The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.Trial registration number NCT05310968.

Long-read genome assemblies reveal a cis-regulatory landscape associated with phenotypic divergence in two sister Siniperca fish species

Due to the difficulty in accurately identifying structural variants(SVs) across genomes,their impact on cisregulato ry diverge n ce of closely related species,especially fish,remains to be explored.Recently identified broad H3K4me3 domains are essential for the regulation of genes involved in several biological processes.However,the role of broad H3K4me3 domains in phenotypic divergence remains poorly understood.Siniperca chuatsi and S.scherzeri are closely related but divergent in several phenotypic traits,making them an ideal model to study cis-regulatory evolution in sister species.Here,we generated chromosome-level genomes of S.chuatsi and S.scherzeri,with assembled genome sizes of 716.35 and740.54 Mb,respectively.The evolutionary histories of S.chuatsi and S.scherzeri were studied by inferring dynamic changes in ancestral population sizes.To explore the genetic basis of adaptation in S.chuatsi and S.scherzeri,we performed gene family expansion and contraction analysis and identified positively selected genes(PSGs).To investigate the role of SVs in cis-regulatory divergence of closely related fish species,we identified high-quality SVs as well as divergent H3K27ac and H3K4me3 domains in the genomes of S.chuatsi and S.scherzeri.Integrated analysis revealed that cis-regulatory divergence caused by SVs played an essential role in phenotypic divergence between S.chuatsi and S.scherzeri.Additionally,divergent broad H3K4me3 domains were mostly associated with cancer-related genes in S.chuatsi and S.scherzeri and contributed to their phenotypic divergence.

Mini-organs with big impact:Organoids in liver cancer studies

Hepatocellular carcinoma,the most common primary liver cancer and a leading cause of death,is a difficult disease to treat due to its heterogeneous nature.Traditional models,such as 2D culture and patient-derived xenografts,have not proven effective.However,the development of 3D culture techniques,such as organoids,which can mimic the tumor microenvironment(TME)and preserve heterogeneity and pathophysiological properties of tumor cells,offers new opportunities for treatment and research.Organoids also have the potential for biomarker detection and personalized medication,as well as genome editing using CRISPR/Cas9 to study the behavior of certain genes and therapeutic interventions.This review explores to-the-date development of organoids with a focus on TME modeling in 3D organoid cultures.Further,it discusses gene editing using CRISPR/Cas9 in organoids,the challenges faced,and the prospects in the field of organoids.

Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial

Background The superiority of balloon angioplasty plus aggressive medical management(AMM)to AMM alone for symptomatic intracranial artery stenosis(sICAS)on efficacy and safety profiles still lacks evidence from randomised controlled trials(RCTs).Aim To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS.Design Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis(BASIS)trial is a multicentre,prospective,randomised,open-label,blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS.Patients eligible in BASIS were 35–80 years old,with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis(70%–99%)of a major intracranial artery.The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio.Both groups will receive identical AMM,including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy,intensive risk factor management and life-style modification.All participants will be followed up for 3years.Study outcomes Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up,or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment,is the primary outcome.Discussion BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients,which may provide an alternative perspective for treating sICAS.Trial registration number NCT03703635;https://www.clinicaltrials.gov.

Emerging personalized virtual brain models: next-generation resection neurosurgery for drug-resistant epilepsy?

Recently,a novel workflow known as the virtual epileptic patient(VEP)has been proposed by a research team from Aix Marseille Universitéin their papers published in Lancet Neurology,Science Translational Medicine and Epilepsia.This method involves creating an individualized virtual brain model based on computational modelling,which can facilitate clinical decision-making by estimating the epileptogenic zone and performing the virtual surgery.Here,we summarize brief workflow,strengths,and limitations of VEP,as well as its performance in a retrospective study of 53 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography.A large-scale clinical trial(NCT03643016)is underway to further assess VEP,which is expected to enroll 356 patients prospectively.As supporting evidence accumulates,the clinical application of VEP has the potential to improve clinical practice,leading to better outcomes and qualities of life of patients.

Tenecteplase versus alteplase for acute ischaemic stroke:a meta-analysis of phaseⅢrandomised trials

Background Tenecteplase(TNK)was found non-inferior to alteplase in recent clinical trials.We aimed to elucidate the efficacy and safety of TNK versus alteplase for acute ischaemic stroke(AIS).Methods Systematic literature search and a meta-analysis of phaseⅢclinical trials in ischaemic stroke patients with TNK use were conducted.The primary outcome was excellent functional outcome which was defined as modified Rankin Scale score of 0–1 at 90 days and safety outcomes included symptomatic intracerebral haemorrhage and death at 90 days.We used random-effects model to estimate the pooled risk difference and 95%CI in R package‘Meta’.The included trials were adapted to the non-inferiority analysis with a margin of-4%.Results Three trials enrolling 4094 patients were identified by systematic search.All trials included AIS patients within 4.5hours time window.Meta-analysis indicated that 1089(53.0%)of 2056 patients in the TNK arm and 1016(50.5%)of 2012 in the alteplase arm had excellent functional outcome at 90 days(0.03(95%CI-0.00 to 0.06);I^(2)=0%),meeting the prespecified non-inferiority threshold.And TNK thrombolysis was not correlated with increased risk of symptomatic intracerebral haemorrhage(0.00(95%CI-0.01 to 0.01);I^(2)=0%)or death(0.01(95%CI-0.01 to 0.02);I^(2)=0%)at 90 days.The sensitivity analysis with the 0.25mg/kg trials exclusively showed similar results to the main analysis.Conclusions TNK was non-inferior to alteplase for achieving excellent functional outcome at 90 days without increasing the safety concern in treating patients with AIS.These findings suggest that TNK can be an alternative to alteplase.

Dynamic Organization of Large-scale Functional Brain Networks Supports Interactions Between Emotion and Executive Control

Emotion and executive control are often conceptualized as two distinct modes of human brain functioning.Little,however,is known about how the dynamic organization of large-scale functional brain networks that support flexible emotion processing and executive control,especially their interactions.The amygdala and prefrontal systems have long been thought to play crucial roles in these processes.Recent advances in human neuroimaging studies have begun to delineate functional organization principles among the large-scale brain networks underlying emotion,executive control,and their interactions.Here,we propose a dynamic brain network model to account for interactive competition between emotion and executive control by reviewing recent resting-state and task-related neuroimaging studies using network-based approaches.In this model,dynamic interactions among the executive control network,the salience network,the default mode network,and sensorimotor networks enable dynamic processes of emotion and support flexible executive control of multiple processes;neural oscillations across multiple frequency bands and the locus coeruleus−norepinephrine pathway serve as communicational mechanisms underlying dynamic synergy among large-scale functional brain networks.This model has important implications for understanding how the dynamic organization of complex brain systems and networks empowers flexible cognitive and affective functions.

Decoding the evolution and transmissions of the novel pneumonia coronavirus(SARS-CoV-2/HCoV-19)using whole genomic data

The outbreak of COVID-19 started in mid-December2019 in Wuhan, China. Up to 29 February 2020,SARS-CoV-2(HCoV-19/2019-nCoV) had infected more than 85 000 people in the world. In this study,we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak.We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau(τ)using the formula t=τ/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes.Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes(31 found in samples from China and 31 from outside China)were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome(bat-RaTG13-CoV)as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes,and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore,phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.

An optical brain-to-brain interface supports rapid information transmission for precise locomotion control

Brain-to-brain interfaces(BtBIs) hold exciting potentials for direct communication between individual brains. However,technical challenges often limit their performance in rapid information transfer. Here, we demonstrate an optical brain-to-brain interface that transmits information regarding locomotor speed from one mouse to another and allows precise, real-time control of locomotion across animals with high information transfer rate. We found that the activity of the genetically identified neuromedin B(NMB) neurons within the nucleus incertus(NI) precisely predicts and critically controls locomotor speed. By optically recording Ca2+ signals from the NI of a "Master" mouse and converting them to patterned optogenetic stimulations of the NI of an "Avatar" mouse, the Bt BI directed the Avatar mice to closely mimic the locomotion of their Masters with information transfer rate about two orders of magnitude higher than previous Bt BIs. These results thus provide proof-of-concept that optical Bt BIs can rapidly transmit neural information and control dynamic behaviors across individuals.

BOPl Silencing Suppresses Gastric Cancer Proliferation through p53 Modulation

Block of proliferation 1(BOP1)is a key protein involved in ribosome maturation and affects cancer progression.However,its role in gastric cancer(GC)remains unknown.This study aimed to explore the expression of BOPI in GC and its potential mechanisms in regulating GC growth,and the relationship between BOP1 level in cancer tissues and survival was also analyzed.The expression of BOPI was examined by immunohistochemistry(IHC)in a cohort containing 387 patients with primary GC.Cultured GC cells were treated by siRNA to knock down the BOP1 expression,and examined by CCK-8 assay and plate clone formation to assess cell proliferation in vitro.Apoptotic rate of cultured GC cells was detected by flow cytometry with double staining of AnnxinV/PI.The xenografted mouse model was used to assess GC cell proliferation in vivo.Western blot and IHC were also performed to detect the expression levels of BOP1,p53 and p21.Patients with higher level of BOP1 in cancer tissues had significantly poorer survival.BOP1 silencing signifcantly suppressed GC cell proliferation both in vitro and in vivo.It blocked cell cycle at G0/G1 phase and led to apoptosis of GC cells via upregulating p53 and p21.BOP1 silencing-induced suppression of cell proliferation was partly reversed by pifithrin-a,(a p53 inhibitor).Our study dermonstrated that BOP1 up-regulation may be a hallmark of GC and it may regulate proliferation of GC cells by activating p53.BOP1 might be considered a novel biomarker of GC proliferation,and could be a potential indicator of prognosis of GC patients.BOP1 might also be a potential target for the treatment of GC patients if further researched.

Transferrin receptor 1 plays an important role in muscle development and denervation-induced muscular atrophy

Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood.In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve.RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated.We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1.The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death.In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation.These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy.This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China(approval No.SYXK 2017-C023) on June 1, 2018.

A User-Friendly SSVEP-Based BCI Using Imperceptible Phase-Coded Flickers at 60Hz

A brain-computer interface(BCI)system based on steady-state visual evoked potentials(SSVEP)was developed by four-class phase-coded stimuli.SSVEPs elicited by flickers at 60Hz,which is higher than the critical fusion frequency(CFF),were compared with those at 15Hz and 30Hz.SSVEP components in electroencephalogram(EEG)were detected using task related component analysis(TRCA)method.Offline analysis with 17 subjects indicated that the highest information transfer rate(ITR)was 29.80±4.65bpm with 0.5s data length for 60Hz and the classification accuracy was 70.07±4.15%.The online BCI system reached an averaged classification accuracy of 87.75±3.50%at 60Hz with 4s,resulting in an ITR of 16.73±1.63bpm.In particular,the maximum ITR for a subject was 80bpm with 0.5s at 60Hz.Although the BCI performance of 60Hz was lower than that of 15Hz and 30Hz,the results of the behavioral test indicated that,with no perception of flicker,the BCI system with 60Hz was more comfortable to use than 15Hz and 30Hz.Correlation analysis revealed that SSVEP with higher signal-to-noise ratio(SNR)corresponded to better classification performance and the improvement in comfortableness was accompanied by a decrease in performance.This study demonstrates the feasibility and potential of a user-friendly SSVEP-based BCI using imperceptible flickers.