Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

于生活一隅窥见平衡之奥妙——由化学平衡到生活中的平衡

用生动的语言,解释了生活中各种不同现象背后所蕴含的平衡、化学平衡的发展历史以及利用平衡所带来的变化,使读者能在轻松惬意的氛围中潜移默化地了解平衡、认识平衡。

3D Printing of Cell-Container-Like Scaffolds for Multicell Tissue Engineering

The development of an engineered non-contact multicellular coculture model that can mimic the in v iv o cell microenvironment of human tissues remains challenging.In this study,we successfully fabricated a cell-container-like scaffold composed of p-tricalcium phosphate/hydroxyapatite(p-TCP/HA)bioceramic that contains four different pore structures,including triangles,squares,parallelograms,and rectangles,by means of three-dimensional(3D)printing technology.These scaffolds can be used to simultaneously culture four types of cells in a non-contact way.An engineered 3D coculture model composed of human bone-marrow-derived mesenchymal stem cells(HBMSCs),human umbilical vein endothelial cells(HUVECs),human umbilical vein smooth muscle cells(HUVSMCs),and human dermal fibroblasts(HDFs)with a spatially controlled distribution was constructed to investigate the individual or synergistic effects of these cells in osteogenesis and angiogenesis.The results showed that three or four kinds of cells cocultured in 3D cell containers exhibited a higher cell proliferation rate in comparison with that of a single cell type.Detailed studies into the cell-cell interactions between HBMSCs and HUVECs revealed that the 3D cell containers with four separate spatial structures enhanced the angiogenesis and osteogenesis of cells by amplifying the paracrine effect of the cocultured cells.Furthermore,the establishment of multicellular non-contact systems including three types of cells and four types of cells,respectively,cocultured in 3D cell containers demonstrated obvious advantages in enhancing osteogenic and angiogenic differentiation in comparison with monoculture modes and two-cell coculture modes.This study offers a new direction for developing a scaffold-based multicellular non-contact coculture system for tissue regeneration.

Automated and refined wetland mapping of Dongting Lake using migrated training samples based on temporally dense Sentinel 1/2 imagery

Wetlands provide vital ecological services for both humans and environment,necessitating continuous,refined and up-to-date mapping of wetlands for conservation and management.in this study,we developed an automated and refined wetland mapping framework integrating training sample migration method,supervised machine learning and knowledge-driven rules using Google Earth Engine(GEE)platform and open-source geospatial tools.We applied the framework to temporally dense Sentinel-1/2 imagery to produce annual refined wetland maps of the Dongting Lake Wetland(DLW)during 2015-2021.First,the continuous change detection(CCD)algorithm was utilized to migrate stable training samples.Then,annual 10 m preliminary land cover maps with 9 classes were produced using random forest algorithm and migrated samples.Ultimately,annual 10 m refined wetland maps were generated based on preliminary land cover maps via knowledge-driven rules from geometric features and available water-related inventories,with Overall Accuracy(OA)ranging from 81.82%(2015)to 93.84%(2020)and Kappa Coefficient(KC)between 0.73(2015)and 0.91(2020),demonstrating satisfactory performance and substantial potential for accurate,timely and type-refined wetland mapping.Our methodological framework allows rapid and accurate monitoring of wetland dynamics and could provide valuable information and methodological support for monitoring,conservation and sustainable development of wetland ecosystem.

The applications of wearable devices in the rehabilitation of ankle injuries: A systematic review and meta-analysis

Wearable devices have been used in the treatment and rehabilitation of ankle injuries.This article systematically reviewed the trials that summarize and evaluate the effectiveness of rehabilitation treatment after an ankle injury.Three databases,PubMed(1974–2021),Embase,and Web of Science(1950–2021),were searched.The intervention was any wearable device,and the outcome measures were Activities Scale for Kids performance(ASKp),Foot and Ankle Outcome Score(FAOS),American Orthopaedic Foot and Ankle Society(AOFAS),Olerud-Molander Ankle Score(OMAS),and Circumference as measured by any validated outcome measure.Two independent authors evaluated the studies with the Cochrane risk-of-bias tool.Four papers were included,involving 476 participants,with a mean age of 29.3±6.7 years.The mean duration of wearable devices was 3.83 weeks,and the mean length of training was 3.75 weeks.Wearable devices achieved better results compared with control on the functional performance(standardized mean difference[SMD]0.66;95%confidence interval[CI]0.29 to 1.04;I^(2)=76%;P<0.001),as well as ankle score(SMD 0.78;95%CI 0.22 to 1.35;I^(2)=82%;P<0.001).The definitive judgment could not be made due to the variability in training,training duration,and outcomes measurement.Wearable devices are a promising approach that has positive effects on ankle injuries in terms of functional performance and reducing the extent of swelling.There is insufficient evidence from randomized controlled trials(RCTs)to support this for ankle injury patients using wearable devices.Therefore,there is an need for well-conducted randomized controlled trials investigating more adaptive orthoses to achieve more effective strategies for early functional rehabilitation.PROSPERO registration number:CRD42021246289.

Crosslinking strategies for preparation of extracellular matrix-derived cardiovascular scaffolds

Heart valve and blood vessel replacement using artificial prostheses is an effective strategy for the treatment of cardiovascular disease at terminal stage.Natural extracellular matrix(ECM)-derived materials(decellularized allogeneic or xenogenic tissues)have received extensive attention as the cardiovascular scaffold.However,the bioprosthetic grafts usually far less durable and undergo calcification and progressive structural deterioration.Glutaraldehyde(GA)is a commonly used crosslinking agent for improving biocompatibility and durability of the natural scaffold materials.However,the nature ECM and GA-crosslinked materials may result in calcification and eventually lead to the transplant failure.Therefore,studies have been conducted to explore new crosslinking agents.In this review,we mainly focused on research progress of ECM-derived cardiovascular scaffolds and their crosslinking strategies.

Background of crustal movement of Chinese mainland

Based on GPS data during May 1995-March 1998 of 12 IGS stations located in the Chinese mainland and its surrounding areas, the horizontal displacement rates of these IGS stations have been determined. The result can be available to study the background of the crustal tectonic motion in the chinese mainland.

Steroid receptor coactivator-1:The central intermediator linking multiple signals and functions in the brain and spinal cord

The effects of steroid hormones are believed to be mediated by their nuclear receptors(NRs).The p160 coactivator family,including steroid receptor coactivator-1(SRC-1),2 and 3,has been shown to physically interact with NRs to enhance their transactivational activities.Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord.It is not only localized in neurons but also detectable in neuroglial cells(mainly localized in the nuclei but also detectable in the extra-nuclear components).Although the expression of SRC-1 is regulated by many steroids,it is also regulated by some non-steroidal factors such as injury,sound and light.Functionally,SRC-1 has been implied in normal function such as development and ageing,learning and memory,central regulation on reproductive behaviors,motor and food intake.Pathologically,SRC-1 may play a role in the regulation of neuropsychiatric disorders(including stress,depression,anxiety,and autism spectrum disorder),metabolite homeostasis and obesity as well as tumorigenesis.Under most conditions,the related mechanisms are far from elucidation;although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity.Several inhibitors and stimulator of SRC-1 have shown anti-cancer potentials,but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear.Therefore,to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.

Ion therapy of pulmonary fibrosis by inhalation of ionic solution derived from silicate bioceramics

Pulmonary fibrosis(PF)is a chronic and progressively fatal disease,but clinically available therapeutic drugs are limited due to efficacy and side effects.The possible mechanism of pulmonary fibrosis includes the damage of alveolar epithelial cells II(AEC2),and activation of immune cells such as macrophages.The ions released from bioceramics have shown the activity in stimulating soft tissue derived cells such as fibroblasts,endothelia cells and epithelia cells,and regulating macrophage polarization.Therefore,this study proposes an“ion therapy”approach based on the active ions of bioceramic materials,and investigates the therapeutic effect of bioactive ions derived from calcium silicate(CS)bioceramics on mouse models of pulmonary fibrosis.We demonstrate that silicate ions significantly reduce pulmonary fibrosis by simultaneously regulating the functions of AEC2 and macrophages.This result suggests potential clinical applications of ion therapy for lung fibrosis.

Specific bFGF targeting of KIM-1 in ischemic kidneys protects against renal ischemia-reperfusion injury in rats

Renal ischemia-reperfusion(I/R)injury is one of the major causes of acute kidney injury.However,there is still no effective treatment for this disease.Basic fibroblast growth factor(bFGF)has been reported to be beneficial for recovery from ischemic diseases.It is vital to increase the local concentration and reduce the diffusion of bFGF in vivo for renal I/R injury therapy.A targeted growth factor delivery system that responds to specific biological signals in the regenerative environment to guide release has been highlighted in tissue repair.In the present study,a specific peptide was fused with bFGF and called bFGF-kidney injury targeting(KIT-bFGF),and this compound specifically targeted kidney injury molecule-1 both in hypoxic renal HK-2 cells in vitro and ischemic kidneys in vivo after intravenous injection.When administered to rat models of renal I/R injury,KIT-bFGF attenuated renal tubule damage and fibrosis,and promoted functional recovery compared to the effects of native bFGF and the control.We also investigated the mechanism by which KIT-bFGF activated the ERK1/2 and Akt signaling pathways to significantly reduce apoptosis and protect against ischemic injury in the kidney.These results demonstrated that targeted delivery of KIT-bFGF could be an effective strategy for the treatment of renal I/R injury.

Inhibition of the negative effect of high glucose on osteogenic differentiation of bone marrow stromal cells by silicon ions from calcium silicate bioceramics

Human bone marrow stem cells(hBMSCs)are exploited for miscellaneous applications in bone tissue engineering where they are mainly used as seed cells.However,high glucose(HG)environment has negative impacts on the proliferation and osteogenic differentiation of hBMSCs,thus reducing the bone formation in diabetic patients.In our former research works,we discovered that silicon(Si)ions extracted from silicate-based bioceramics are able to stimulate the proliferation and osteogenic differentiation of hBMSCs under normal culture condition.This study aimed to investigate if Si ions could prevent HG-induced inhibition of proliferation and osteogenesis of hBMSCs.We found that 2.59ppm concentration of Si ions promoted the proliferation of hBMSCs under HG condition.The results from alkaline phosphatase(ALP)activity assay,Alizarin red S staining and quantitative real-time PCR analysis of osteogenic genes(BMP2,RUNX2,ALP,COL1 and OCN)demonstrated that the 15.92ppm concentration of Si ions prevented HG-induced inhibition of the osteogenic differentiation of hBMSCs.Moreover,application of Si ions reduced the level of reactive oxygen species in HG-treated hBMSCs.In HG-treated hBMSCs following 15.92ppm Si ions treatment,activation of BMP2/SMAD signaling pathway was detected,as indicated by the increased expression of BMP2 receptors and its downstream genes such as SMAD1,SMAD4 and SMAD5.Taken together,we provide evidence that the specific concentration of Si ions compensated HG-induced inhibition of proliferation and osteogenic differentiation of hBMSCs through antioxidant effect and modulation of BMP2/SMAD pathway.The results suggest that silicate-based bioceramics might be good scaffold biomaterials for bone engineering applications in diabetes patients.

Ambient synthesis, characterization, and electrochemical activity of LiFePO4 nanomaterials derived from iron phosphate intermediates

LiFePO4 materials have become increasingly popular as a cathode material due to the many benefits they possess including thermal stability, durability, low cost, and long life span. Nevertheless, to broaden the general appeal of this material for practical electrochemical applications, it would be useful to develop a relatively mild, reasonably simple synthesis method of this cathode material. Herein, we describe a generalizable, 2-step methodology of sustainably synthesizing LiFePO4 by incorporating a template-based, ambient, surfactantless, seedless, U-tube protocol in order to generate size and morphologically tailored, crystalline, phase-pure nanowires. The purity, composition, crystallinity, and intrinsic quality of these wires were systematically assessed using transmission electron microscopy （TEM）, high-resolution TEM （HRTEM）, scanning electron microscopy （SEM）, X-ray diffraction （XRD）, selected area electron diffraction （SAED）, energy dispersive analysis of X-rays （EDAX）, and high-resolution synchrotron XRD. From these techniques, we were able to determine that there is an absence of any obvious defects present in our wires, supporting the viability of our synthetic approach. Electrochemical analysis was also employed to assess their electrochemical activity. Although our nanowires do not contain any noticeable impurities, we attribute their less than optimal electrochemical rigor to differences in the chemical bonding between our LiFePO4 nanowires and their bulk-like counterparts. Specifically, we demonstrate for the first time experimentally that the Fe-O3 chemical bond plays an important role in determining the overall conductivity of the material, an assertion which is further supported by recent ＂first-principles＂ calculations. Nonetheless, our ambient, solution-based synthesis technique is capable of generating highly crystalline and phase-pure energy-storage-relevant nanowires that can be tailored so as to fabricate different sized materials of reproducible, reliable morphology.