RNA modifications are involved in many aspects of biological functions. N6-methyladenosine (mA) is one of the most important forms of RNA methylation and plays a vital role in regulating gene expression, protein translation, cell behaviors, and physiological conditions in many species, including humans. The dynamic and reversible modification of mA is conducted by three elements: methyltransferases ("writers"), such as methyltransferase-like protein 3 (METTL3) and METTL14; mA-binding proteins ("readers"), such as the YTH domain family proteins (YTHDFs) and YTH domain-containing protein 1 (YTHDC1); and demethylases ("erasers"), such as fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5). In this review, we summarize the current knowledge on mapping mRNA positions of mA modification and revealing molecular processes of mA. We further highlight the biological significance of mA modification in neural cells during development of the nervous system and its association with human diseases. mA RNA methylation is becoming a new frontier in neuroscience and should help us better understand neural development and neurological diseases from a novel point of view.

Summary The catalase family of Beauveria bassiana (fungal entomopathogen) consists of catA (spore‐specific), catB (secreted), catP (peroxisomal), catC (cytoplasmic) and catD (secreted peroxidase/catalase), which were distinguished in phylogeny and structure and functionally characterized by constructing single‐gene disrupted and rescued mutants for enzymatic and multi‐phenotypic analyses. Total catalase activity decreased 89% and 56% in ΔcatB and ΔcatP, corresponding to the losses of upper and lower active bands gel‐profiled for all catalases respectively, but only 9−12% in other knockout mutants. Compared with wild type and complement mutants sharing similar enzymatic and phenotypic parameters, all knockout mutants showed significant (9−56%) decreases in the antioxidant capability of their conidia (active ingredients of mycoinsecticides), followed by remarkable phenotypic defects associated with the fungal biocontrol potential. These defects included mainly the losses of 40% thermotolerance (45°C) in ΔcatA, 46−48% UV‐B resistance in ΔcatA and ΔcatD, and 33−47% virulence to Spodoptera litura larvae in ΔcatA, ΔcatP and ΔcatD respectively. Moreover, the drastic transcript upregulation of some other catalase genes observed in the normal culture of each knockout mutant revealed functionally complimentary effects among some of the catalase genes, particularly between catB and catC whose knockout mutants displayed little or minor phenotypic changes. However, the five catalase genes functioned redundantly in mediating the fungal tolerance to either hyperosmotic or fungicidal stress. The differentiated roles of five catalases in regulating the B. bassiana virulence and tolerances to oxidative stress, high temperature and UV‐B irradiation provide new insights into fungal adaptation to stressful environment and host invasion.

Circular RNAs (circRNAs) are a class of long noncoding RNAs that are characterized by the presence of covalently linked ends, and have been found in all life kingdoms. Exciting studies in regulatory roles of circRNAs are emerging. Here we summarize classification, characteristics, biogenesis and regulatory functions of circRNAs. CircRNAs are found to be preferentially expressed along neural genes and in neural tissues. We thus highlight the association of circRNA dysregulation with neurodegenerative diseases such as Alzheimer’s disease. Investigation of regulatory role of circRNAs will shed novel light in gene expression mechanisms during development and under disease conditions, and may identify circRNAs as new biomarkers for aging and neurodegenerative disorders.

The variable stiffness actuator (VSA) has been equipped on many new generation of robots because of its superior performance in terms of safety, robustness and flexibility. However, the control of robots with joints driven by variable stiffness actuators is challenging due to the inherited highly nonlinear dynamics. In this paper, a novel disturbance observer based adaptive neural network control is developed for robotic systems with variable stiffness joints and subject to model uncertainties. By utilizing a high dimensional integral-type Lyapunov function, adaptive neural network control is designed to approximate the model uncertainties, and a disturbance observer is integrated to compensate for the nonlinear VSA dynamics, as well as the neural network approximation errors and external disturbance. The semiglobally uniformly ultimately boundness of the closedloop control system has been theoretically established. Simulation and extensive experimental studies have also been performed to verify the effectiveness of the proposed approach.

Filamentous fungal insect pathogens represent a source of biological insecticides and acaricides formulated using intact cells, such as conidia or other spores. These mycoinsecticides infect arthropod pests through cuticular penetration. In field application, formulated fungal cells are exposed to environmental stresses, including solar UV irradiation, high temperature, and applied chemical herbicides and fungicides, as well as stress from host immune defenses. These stresses often result in accumulation of toxic reactive oxygen species (ROS), generating oxidative stress to the fungal cells and hence affecting the efficacy and persistency of fungi formulated for pest control. In response, fungi have evolved effective antioxidant mechanisms that include enzyme families that act as ROS scavengers, e.g., superoxide dismutases, catalases, peroxidases, thioredoxins /thioredoxin reductases, and glutaredoxins/glutathione reductases. Over two dozen antioxidant enzymes dispersed in different families have been characterized in Beauveria bassiana in recent years. This mini-review focuses on the progress detailed in the studies of these enzymes and provides an overview of their antioxidant activities and contributions to conidial thermotolerance, UV resistance and virulence. These activities are crucial for the biological control potential of mycoinsecticide formulation and have significantly advanced our understanding of how these organisms work. Several potent antioxidant genes have been exploited for successful genetic engineering of entomopathogenic fungi aimed at enhancing their potential against arthropod pests.

Pil1A and Pil1B are two core eisosome proteins that are homologous to yeast Pil1/Lsp1 or filamentous fungal Pil1A/Pil1B but have been unexplored in entomopathogenic fungi. Here we examined subcellular localization and functions of Pil1A and Pil1B in Beauveria bassiana, a fungal insect pathogen. Either localization or co-localization experiments of the two proteins demonstrated that Pil1A and Pil1B were simultaneously localized at the periphery of hyphal cells for formation of stable, punctuate spots in B. bassiana. This is different from a reliance of proper Lsp1/Pil1B localization upon Pil1/Pil1A in other fungi. Deletions of pil1A and pil1B caused opposite changes in expression of many autophagy-related genes and formation of intravacuolar autophagosomes. Such opposite changes were restored to nearly normal status by exogenous rapamycin, implicating a link of Pil1A/B to the target of rapamycin signalling pathway. All single/double deletion mutants of pil1A and pil1B lost almost all pathogenicity due to reduced ability to secrete Pr1 proteases for cuticle degradation. They also showed differential changes in cell wall integrity and multiple stress responses. These findings unveil opposite roles for Pil1A and Pil1B in autophagic regulation and an essentiality of both for cell integrity, function and pathogenicity of the fungal entomopathogen.

Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding of more enthralling and captivating compounds to suspend and standstill the pathology of NDDs will be considered as a hallmark of present times. Phytochemicals possess the potential to alternate the synthetic line of therapy against NDDs. The present review explores the potential efficacy of plant-derived flavonoids against most common NDDs including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Flavonoids are biologically active phytochemicals which possess potential pharmacological effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic and anti-oxidant effects and are able to attenuate the pathology of various NDDs through down-regulating the nitric oxide (NO) production, by reducing the tumor necrosis factor-α (TNF-α), by reducing the excitotoxicity of superoxide as well as acting as tyrosine kinase (TK) and monoamine oxidase (MAO) inhibiting enzyme.

The eukaryotic calcineurin (CN) pathway comprising catalytic A (CnA) and regulatory B subunits (CnB) is crucial for many biological processes but functionally unexplored in entomopathogenic fungi. Here, we characterise three CN subunits (CnA1, CnA2 and CnB) and a downstream CN-responsive zinc finger transcription factor (Crz1) in Beauveria bassiana. CN-mediated phosphatase activity decreased by 16-38 % in all deletion mutants compared with wild type. Growth and conidiation were most defective in ΔcnB, which showed a large proportion of abnormally branched germlings but were less defective in ΔcnA1 and ΔcnA2. Conidiation defects also occurred in Δcrz1, uniquely accompanied with slower germination. Compared with wild type, the four deletion mutants became, to varying degrees, more sensitive to Ca(2+), Mn(2+), Zn(2+), Mg(2+), two oxidants, three cell wall stressors, carbendazim, heat shock and ultraviolet (UV)-B irradiation. They were also less virulent to Spodoptera litura larvae. Only ΔcnB and Δcrz1 were less tolerant to high osmolarity. The altered phenotypes of the deletion mutants were associated with lower intracellular mannitol and trehalose levels, reduced overall activity of superoxide dismutases and catalases, altered cell wall composition and down-regulation of numerous phenotype-influencing genes. Additionally, the transcription of six cascaded genes in two stress-responsive mitogen-activated protein kinase (MAPK) pathways and the phosphorylation of hallmarking Hog1 and Slt2 were largely down-regulated in all the deletion mutants under osmotic and cell wall stresses, respectively. All the changes were restored by gene complementation. Taken together, three calcineurin subunits and Crz1 play vital, but variable, roles in B. bassiana responses to environmental stresses during development and host signals during infection.