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Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo . In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneities in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.

Xiong'an New Area boasts abundant geothermal resources, with widespread Jixianian geothermal reservoirs serving as key targets for exploration and development. Zoning geothermal resources helps characterize their distribution and attributes, offering critical guidance for their sustainable exploitation and utilization. This study integrates data from drilling and production tests across 21 geothermal wells to analyze the Jixianian strata, including depth, thickness, temperature, single-well water yield, Groundwater Level Depth (GWD), and Total Dissolved Solids (TDS). Employing fuzzy mathematics, a zoning analysis was performed, yielding quantitative evaluation scores and delineating favorable zones for development. Key findings include: (1) Geothermal reservoirs in the Rongcheng and Niutuozhen uplifts exhibit shallow burial depths, substantial thicknesses, high productivity, and relatively low temperatures, making them highly suitable for large-scale geothermal exploitation; (2) Zones with high resource potential but uncertain conditions require further exploration to mitigate development risks; (3) Areas near the Rongcheng fault or Jixianian strata buried deeper than 4,000 m are recommended for deferred exploitation; (4) Comprehensive evaluation reveals that the Jixianian carbonate geothermal reservoirs in Xiong'an New Area manifest geothermal resources of 5,370.31×1016 J, geothermal fluid reserves of 101.17×108 m3, and recoverable fluid reserves of 93.41×104 m3/d under balanced extraction and reinjection. Recoverable geothermal heat amounts to 9.36×1016 J/a, equivalent to 319.4×104 t/a of standard coal. This study provides valuable insights into the exploration and sustainable exploitation of deep geothermal reservoirs in Xiong'an New Area, enhancing resource utilization and contributing to the development of a green and sustainable Xiong'an New Area.

Background. Tai Chi (TC) is known to enhance balance control and walking function in stroke survivors. However, motor disorders in stroke patients may limit the implementation of TC exercise and increase the risk of falling. The body weight support (BWS) device can provide protection during the early rehabilitation of stroke survivors using an overhead suspension system. Theoretically, combining TC with BWS may be an effective intervention for stroke survivors. This study aimed to examine the effects of body weight support-Tai Chi training on balance control and walking function in stroke survivors with hemiplegia. Methods. Seventy-one stroke survivors with hemiplegia aged 30–75 years were randomly allocated to the control group (N = 35) or the BWS-TC group (N = 36). During BWS-TC training, the subjects performed 7 Tai Chi footwork forms, and gradual easy-to-difficult progression (from 40% to 0% body weight) was followed. The subjects participated in 40 min rehabilitation sessions three times per week for 12 weeks. The primary outcome was dynamic balance in the limits-of-stability test. The secondary outcomes, which reflect improvements walking function, included spatiotemporal parameters, the joint range of motion in the affected limb during the swing phase, the Berg Balance Scale score, and the Fugl-Meyer Assessment score. Evaluations were performed at baseline and 12 weeks and compared between groups. Results. After training, significant between-group differences were observed in the scores for overall, forward, left, right, forward-left, and forward-right directional control in the limits-of-stability test (P<0.05). Furthermore, the scores for gait cycle time, step length, step velocity, and range of motion of the joints were better in the BWS-TC group than in the control group (P<0.05). Conclusions. The 12-week BWS-TC training may enhance dynamic balance and walking function in stroke survivors with hemiplegia.

Background Transcranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). Methods This study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase. Discussion The study’s findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment. Trial registration Chinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.

IntroductionOur previous studies have proposed the bodyweight support–t’ai chi (BWS-TC) footwork training for stroke survivors with severe motor dysfunction and fear of falling, and have proven its positive effects for motor function. Transcranial direct current stimulation (tDCS) provides a non-invasive and safe way to modulate neuronal activity and provoke neuroplastic changes and to improve the motor function of stroke survivors. However, it is unclear whether the integration of BWS-TC and tDCS has synergistic effects on improving motor function of the stroke survivors.Methods and analysisThis study will be an assessor-blinded randomised controlled trial involving 12-week intervention and 6-month follow-up. One hundred and thirty-five individuals with stroke will be randomly divided in a ratio of 1:1:1 into three groups. Control group A, control group B and intervention group C will receive tDCS and conventional rehabilitation programmes (CRPs), BWS-TC and CRP, tDCS-BWS-TC and CRP for 12 weeks, respectively. The primary outcome measures will include the efficacy (Fugl-Meyer Assessment), acceptability and safety of these interventions. The secondary outcome measures will include balance ability (ie, limits of stability and modified clinical test of sensory integration), walking function, brain structure and function, risk of falling, Barthel Index and 36-Item Short Form Survey. All outcomes will be assessed at baseline, 6 and 12 weeks during intervention, and 1, 3 and 6 months during the follow-up period. Two-way analysis of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group–time interaction effects for all outcome measures.Ethics and disseminationEthics approval was obtained from the ethics committee of the Shanghai Seventh People’s Hospital (2021-7th-HIRB-017). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences.Trial registration numberChiCTR2200059329.