Effect of Ba-Duan-Jin on Immune Function and Autonomic Nervous Balance in Ageing People

[Objective] Ba-Duan-Jin, formed in the 12th century, is an excellent traditional Chinese health exercises. Ancients likened it to “brocade (Jin)”, meaning its action is as elegant as brocade. The total movements are divided into 8 sections, so it is called “ Ba-Duan-Jin (8-section-action)”. Because of its simple action and significantly healthy effect, Ba-Duan-Jin is widely used to enhance physical fitness and prevent diseases. This study was aimed to evaluate the immunological effect of Ba-Duan-Jin in ageing people and analyze its autonomic nervous mechanism. [Methods] 60 healthy women (64.06±2.53 years old) were divided into exercising group and sedentary group. Exercising group trained Ba-Duan-Jin 12 weeks（5 day/week, 3 repetition/day）. Record electrocardiosignal to analyze heart rate variability (HRV) , and then take blood sample to measure blood routine, immune globulin, complement, sub-T lymphocyte, catecholamines and acetylcholine. These measurements were performed before and after the 8-week’s intervening duration. [Results] The plasma immune globulin, complement, catecholamines and acetylcholine have no significant difference between two groups. But when it came to lymphocyte in peripheral blood, the women in exercising group have less CD8+ T-lymphocyte and higher rate of CD4+/CD8+ than sedentary group. The analysis of HRV showed an increasing total HRV (TF), a enhanced activity of parasympathetic nerve (RRmean, SDNN, RMSSD, HFnorm) and an attenuated activity of sympathetic nerve (LFnorm) in Ba-Duan-Jin exercising group. Correlation analysis confirmed that there is a close relationship between immune function and autonomic nervous activities. [Conclusion] Ba-Duan-Jin can transfer the autonomic nervous balance to parasympathetic dominance, which may partially explain the increasing immunity function (especially in cell immunity) in ageing people. Fig: the 8 sections of Ba-Duan-Jin Note: 1. Holding heaven in the palms2. Posing as an archer shooting3. Holding one arm aloft4. Looking backward5. Swinging the head and lowering the body6. Moving the hands down the back and legs, and touching the Feet7. Thrusting the fists and making the eyes glare8. Raising and Lowering the Heel

Electromagnetic Spatiotemporal Differentiators

Spatiotemporal optical computing devices which could perform mathematical operations in both spatial and temporal domains can provide unprecedented measures to build efficient and real-time information processing systems. It is particularly important to realize the comprehensive functions in a compact design for better integration with electronic components. In this work, we experimentally demonstrated an analogue spatiotemporal differentiator in microwaves based on an asymmetrical metasurface which has a phase singularity in the spatiotemporal domain. We showed that this structure could give rise to a spatiotemporal transfer function required by an ideal first-order differentiator in both spatial and temporal domains by tailoring the unidirectional excitation of spoof surface plasmon polaritons (SSPPs). The spatial edge detection was performed utilizing a metallic slit and the temporal differentiation capability of the device was examined by Gaussian-like temporal pulses of different width. We further confirmed the differentiator demonstrated here could detect sharp changes of spatiotemporal pulses even with intricate profiles and theoretically estimated the resolution limits of the spatial and temporal edge detection. We also show that the pulse input after passing the spatiotemporal differentiator implemented here could carry a transverse orbital angular momentum (OAM) with a fractal topology charge which further increases the information quantity.Comment: 6 figure

Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the abnormal accumulation of amyloid plaques and hyperphosphorylated tau aggregates, as well as microgliosis. Hemizygous missense variants in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with elevated risk for developing late-onset AD. These variants are hypothesized to result in loss of function, mimicking TREM2 haploinsufficiency. However, the consequences of TREM2 haploinsufficiency on tau pathology and microglial function remain unknown. We report the effects of partial and complete loss of TREM2 on microglial function and tau-associated deficits. In vivo imaging revealed that microglia from aged TREM2-haploinsufficient mice show a greater impairment in their injury response compared with microglia from aged TREM2-KO mice. In transgenic mice expressing mutant human tau, TREM2 haploinsufficiency, but not complete loss of TREM2, increased tau pathology. In addition, whereas complete TREM2 deficiency protected against tau-mediated microglial activation and atrophy, TREM2 haploinsufficiency elevated expression of proinflammatory markers and exacerbated atrophy at a late stage of disease. The differential effects of partial and complete loss of TREM2 on microglial function and tau pathology provide important insights into the critical role of TREM2 in AD pathogenesis

Size‐Dependent Photocatalytic Reactivity of Conjugated Microporous Polymer Nanoparticles

Particle size is a critical factor for improving photocatalytic reactivity of conjugated microporous polymers (CMPs) as mass transfer in the porous materials is often the rate‐limiting step. However, due to the synthetic challenge of controlling the size of CMPs, the impact of particle size is yet to be investigated. To address this problem, a simple and versatile dispersion polymerization route that can synthesize dispersible CMP nanoparticles with controlled size from 15 to 180 nm is proposed. Leveraging the precise control of the size, it is demonstrated that smaller CMP nanoparticles have dramatically higher photocatalytic reactivity in various organic transformations, achieving more than 1000% enhancement in the reaction rates by decreasing the size from 180 to 15 nm. The size‐dependent photocatalytic reactivity is further scrutinized using a kinetic model and transient absorption spectroscopy, revealing that only the initial 5 nm‐thick surface layer of CMP nanoparticles is involved in the photocatalytic reactions because of internal mass transfer limitations. This finding substantiates the potential of small CMP nanoparticles to efficiently use photo‐generated excitons and improve energy‐efficiency of numerous photocatalytic reactions

Fibrinogen inhibits sonic hedgehog signaling and impairs neonatal cerebellar development after blood-brain barrier disruption.

Cerebellar injury in preterm infants with central nervous system (CNS) hemorrhage results in lasting neurological deficits and an increased risk of autism. The impact of blood-induced pathways on cerebellar development remains largely unknown, so no specific treatments have been developed to counteract the harmful effects of blood after neurovascular damage in preterm infants. Here, we show that fibrinogen, a blood-clotting protein, plays a central role in impairing neonatal cerebellar development. Longitudinal MRI of preterm infants revealed that cerebellar bleeds were the most critical factor associated with poor cerebellar growth. Using inflammatory and hemorrhagic mouse models of neonatal cerebellar injury, we found that fibrinogen increased innate immune activation and impeded neurogenesis in the developing cerebellum. Fibrinogen inhibited sonic hedgehog (SHH) signaling, the main mitogenic pathway in cerebellar granule neuron progenitors (CGNPs), and was sufficient to disrupt cerebellar growth. Genetic fibrinogen depletion attenuated neuroinflammation, promoted CGNP proliferation, and preserved normal cerebellar development after neurovascular damage. Our findings suggest that fibrinogen alters the balance of SHH signaling in the neurovascular niche and may serve as a therapeutic target to mitigate developmental brain injury after CNS hemorrhage

AD-linked R47H-TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation

The hemizygous R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific gene in the brain, increases risk for late-onset Alzheimer’s disease (AD). Using transcriptomic analysis of single nuclei from brain tissues of patients with AD carrying the R47H mutation or the common variant (CV)–TREM2, we found that R47H-associated microglial subpopulations had enhanced inflammatory signatures reminiscent of previously identified disease-associated microglia (DAM) and hyperactivation of AKT, one of the signaling pathways downstream of TREM2. We established a tauopathy mouse model with heterozygous knock-in of the human TREM2 with the R47H mutation or CV and found that R47H induced and exacerbated TAU-mediated spatial memory deficits in female mice. Single-cell transcriptomic analysis of microglia from these mice also revealed transcriptomic changes induced by R47H that had substantial overlaps with R47H microglia in human AD brains, including robust increases in proinflammatory cytokines, activation of AKT signaling, and elevation of a subset of DAM signatures. Pharmacological AKT inhibition with MK-2206 largely reversed the enhanced inflammatory signatures in primary R47H microglia treated with TAU fibrils. In R47H heterozygous tauopathy mice, MK-2206 treatment abolished a tauopathy-dependent microglial subcluster and rescued tauopathy-induced synapse loss. By uncovering disease-enhancing mechanisms of the R47H mutation conserved in human and mouse, our study supports inhibitors of AKT signaling as a microglial modulating strategy to treat AD

Selective targeting of microglia by quantum dots

<p>Abstract</p> <p>Background</p> <p>Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.</p> <p>Methods</p> <p>Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.</p> <p>Results</p> <p>In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.</p> <p>Conclusions</p> <p>These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.</p

Corrigendum to: The TianQin project: current progress on science and technology

In the originally published version, this manuscript included an error related to indicating the corresponding author within the author list. This has now been corrected online to reflect the fact that author Jun Luo is the corresponding author of the article