Underlying mechanisms and clinical potential of circRNAs in glioblastoma

Glioblastoma(GBM)is the most malignant form of glioma and is difficult to diagnose,leading to high mortality rates.Circular RNAs(circRNAs)are noncoding RNAs with a covalently closed loop structure.CircRNAs are involved in various pathological processes and have been revealed to be important regulators of GBM pathogenesis.CircRNAs exert their biological effects by 4 different mechanisms:serving as sponges of microRNAs(miRNAs),serving as sponges of RNA binding proteins(RBPs),modulating parental gene transcription,and encoding functional proteins.Among the 4 mechanisms,sponging miRNAs is predominant.Their good stability,broad distribution and high specificity make circRNAs promising biomarkers for GBM diagnosis.In this paper,we summarized the current understanding of the characteristics and action mechanisms of circRNAs,illustrated the underlying regulatory mechanisms of circRNAs in GBM progression and explored the possible diagnostic role of circRNAs in GBM.

Effect of the Gut Microbiota on Obesity and Its Underlying Mechanisms: an Update

Obesity has become one of the most prevalent health issues of our time. According to a 2012 WHO report, around 3.4 million adults die each year as a result of being overweight or obese. Humans are in fact superorganisms composed of both human and microbial cells with 2 sets of genes, those encoded in our own genome and those encoded in our microbiota. All these cells and genes have the potential to influence our health.

Additive manufacturing of magnesium and its alloys: process-formabilitymicrostructure-performance relationship and underlying mechanism

Magnesium and its alloys,as a promising class of materials,is popular in lightweight application and biomedical implants due to their low density and good biocompatibility.Additive manufacturing(AM)of Mg and its alloys is of growing interest in academia and industry.The domain-by-domain localized forming characteristics of AM leads to unique microstructures and performances of AM-process Mg and its alloys,which are different from those of traditionally manufactured counterparts.However,the intrinsic mechanisms still remain unclear and need to be in-depth explored.Therefore,this work aims to discuss and analyze the possible underlying mechanisms regarding defect appearance and elimination,microstructure formation and evolution,and performance improvement,based on presenting a comprehensive and systematic review on the relationship between process parameters,forming quality,microstructure characteristics and resultant performances.Lastly,some key perspectives requiring focus for further progression are highlighted to promote development of AM-processed Mg and its alloys and accelerate their industrialization.

An evaluation of underlying mechanisms for“fishing down marine food webs”

Since the concept of ＂fishing down marine food webs＂ was first proposed in 1998, mean trophic level of fisheries landings（MTL） has become one of the most widely used indicators to assess the impacts of fishing on the integrity of marine ecosystem and guide the policy development by many management agencies. Recent studies suggest that understanding underlying causes for changes in MTL is vital for an appropriate use of MTL as an indicator of fishery sustainability. Based on the landing data compiled by Food and Agriculture Organization（FAO） and trophic information of relevant species in Fishbase, we evaluated MTL trends in 14 FAO fishing areas and analyzed catches of upper and lower trophic level groups under different trends of MTL and found that both the cases of a recovered MTL trend and a generally increasing MTL trend could be accompanied by decreasing catches of lower trophic level species. Further, community structure and exploitation history should be considered in using MTL after excluding species with trophic levels lower than 3.25 to distinguish ＂fishingthrough＂ from ＂fishing-down＂. We conclude that MTL used as an indicator to measure fishery sustainability can benefit from a full consideration of both upper and lower trophic level species and masking effects of community structure and exploitation history.

Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism

Alzheimer’s disease（AD）is a neurodegenerative disorder which is remarkably characterized by pathological hallmarks that include neurofibrillary tangles,neuronal loss extracellular senile plaques containing aggregated amyloid beta（Aβ）,and neurofibrillary tangles composed of the hyperphosphorylated form of the microtubule protein tau.It is the most common form of dementia which is characterized by severe neurodegenerative changes such as loss of neurons and synapses in brain（Kamat et al.,2014）.

Toxic effects of metal oxide nanoparticles and their underlying mechanisms

Nanomaterials have attracted considerable interest owing to their unique physicochemical properties.The wide application of nanomaterials has raised many concerns about their potential risks to human health and the environment.Metal oxide nanopartides（MONPs）,one of the main members of nanomaterials,have been applied in various fields,such as food,medicine,cosmetics,and sensors.This review highlights the bio-toxic effects of widely applied MONPs and their underlying mechanisms.Two main underlying toxicity mechanisms,reactive oxygen species（ROS）-and non-ROS-mediated toxidties,of MONPs have been widely accepted.ROS activates oxidative stress,which leads to lipid peroxidation and cell membrane damage.In addition,ROS can trigger the apoptotic pathway by activating caspase-9 and-3.Non-ROS-mediated toxicity mechanism includes the effect of released ions,excessive accumulation of NPs on the cell surface,and combination of NPs with specific death receptors.Furthermore,the combined toxicity evaluation of some MONPs is also discussed.Toxicity may dramatically change when nanomaterials are used in a combined system because the characteristics of NPs that play a key role in their toxicity such as size,surface properties,and chemical nature in the complex system are different from the pristine NPs.

Computational Model for the Underlying Mechanisms Regulating Bone Loss by Mechanical Unloading and Estrogen Deficiency

The objective of this paper is to investigate the different effects of disuse and estrogen deficiency on bone loss and the underlying mechanisms.A mechanical-biological factors coupled computational model was built to simulate different patterns of bone loss induced in female rats by hind limb unloading,ovariectomy,or both in an animal study.A remodeling analysis was performed on a representative cross section of 6 mm2 of cancellous bone in the distal femoral metaphysis of the rats.The BMU activation frequency,the refilling rate,and the principal compressive strain in the state of mechanical unloading and estrogen deficiency were simulated to interpret the underlying mechanisms.Simulated bone loss patterns due to mechanical unloading,estrogen deficiency,or both all corresponded with the experimental observations.The results show that mechanical unloading and estrogen deficiency cause different bone loss patterns;moreover,mechanical unloading induces a greater degree of bone loss than estrogen deficiency,which can lead to improved treatment and prevention strategies for osteoporosis.

Revealing the underlying mechanisms behind TE extraordinary THz transmission

Transmission through seemingly opaque surfaces,so-called extraordinary transmission,provides an exciting platform for strong light–matter interaction,spectroscopy,optical trapping,and color filtering.Much of the effort has been devoted to understanding and exploiting TM extraordinary transmission,while TE anomalous extraordinary transmission has been largely omitted in the literature.This is regrettable from a practical point of view since the stronger dependence of the TE anomalous extraordinary transmission on the array’s substrate provides additional design parameters for exploitation.To provide high-performance and cost-effective applications based on TE anomalous extraordinary transmission,a complete physical insight about the underlying mechanisms of the phenomenon must be first laid down.To this end,resorting to a combined methodology including quasi-optical terahertz(THz)time-domain measurements,full-wave simulations,and method of moments analysis,subwavelength slit arrays under s-polarized illumination are studied here,filling the void in the current literature.We believe this work unequivocally reveals the leaky-wave role of the grounded-dielectric slab mode mediating in TE anomalous extraordinary transmission and provides the necessary framework to design practical high-performance THz components and systems.

Glial Activation, A Common Mechanism Underlying Spinal Synaptic Plasticity？

Long-term potentiation （LTP） at synapses between primary afferents and spinal dorsal horn neurons induced by noxious electrical stimulation or injury of peripheral nerve is con- sidered to underlie chronic pain [1]. The mechanisms of the spinal LTP have been intensively investigated, since it was discovered in 1995 [2]. In recent years, spinal application of ATP [3], brain-derived neurotrophic factor （BDNF） [4] and opioid [5] has been shown to induce spinal LTP at C-fiber synapses in the absence of conditioning activation of primary afferents. This is contrary to the general belief that coinci- dent pre- and postsynaptic activity is needed for LTP induction. Recently, Sandkiihler and his co-workers reported in Science that combined activation of microglia and astro- cytes by P2X7 receptor agonist BzATP induces LTP at synapses between afferent C-fibers and spinal lamina I neurons in the absence of presynaptic activation, which is termed gliogenic LTP [6] （Fig. 1C）. To determine the rela- tionship between the gliogenic LTP and high frequency stimulation （HFS）-indueed LTP, they used transverse lum- bar spinal cord slices with long dorsal roots which were separated into halves. Twenty two lamina I neurons that received independent monosynaptic C-fiber inputs from each dorsal root half were recorded. Homosynaptic LTP is recorded in 12 neurons, among them 6 neurons also show heterosynaptic LTP （Fig. 1A）. Interestingly, heterosynaptic LTP is also induced in 5 neurons in which HFS fails to induce homosynaptic LTP （Fig. 1B）.

Researchers revealed a neural mechanism underlying body temperature regulation

Subject Code:C09 With the support by the National Natural Science Foundation of China,a research group led by Dr.Shen Wei(沈伟)from Shanghai Tech University has deconstructed a neural circuit for body temperature regulation,which was published in PNAS(2017,114:2042—2047).

Controlled release of hydrogen by implantation of magnesium induces P53-mediated tumor cells apoptosis

Hydrogen has been used to suppress tumor growth with considerable efficacy.Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration.We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials.However,the underlying mechanism of hydrogen’s role in cancer treatment remains ambiguous.Here,we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials.We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins,as demonstrated by the in vitro RNA sequencing and protein expression analysis.Then,the P53 proteins disrupt the membrane potential of mitochondria,activate autophagy,suppress the reactive oxygen species in cancer cells,and finally result in tumor suppression.The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse.We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2μL/mm^(3)per day,which is much lower than that required for hydrogen inhalation.Taken together,these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway,which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.