The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.

Two-Stage IoT Computational Task Offloading Decision-Making in MEC with Request Holding and Dynamic Eviction

The rapid development of Internet of Things(IoT)technology has led to a significant increase in the computational task load of Terminal Devices(TDs).TDs reduce response latency and energy consumption with the support of task-offloading in Multi-access Edge Computing(MEC).However,existing task-offloading optimization methods typically assume that MEC’s computing resources are unlimited,and there is a lack of research on the optimization of task-offloading when MEC resources are exhausted.In addition,existing solutions only decide whether to accept the offloaded task request based on the single decision result of the current time slot,but lack support for multiple retry in subsequent time slots.It is resulting in TD missing potential offloading opportunities in the future.To fill this gap,we propose a Two-Stage Offloading Decision-making Framework(TSODF)with request holding and dynamic eviction.Long Short-Term Memory(LSTM)-based task-offloading request prediction and MEC resource release estimation are integrated to infer the probability of a request being accepted in the subsequent time slot.The framework learns optimized decision-making experiences continuously to increase the success rate of task offloading based on deep learning technology.Simulation results show that TSODF reduces total TD’s energy consumption and delay for task execution and improves task offloading rate and system resource utilization compared to the benchmark method.

m6A修饰对中枢神经系统功能及疾病的影响

6-甲基腺嘌呤(N6-methyladenosine,m6A)是一种重要的RNA修饰,参与细胞内mRNA的整个代谢活动,调控基因的表达,调节多种生物过程,在大脑组织中丰度较高。稳定的m6A修饰有助于胚胎大脑发育、记忆力的形成,在维持中枢神经系统的功能中起到重要作用。当m6A修饰水平及相关蛋白表达水平发生改变时,将会引起神经系统功能异常,包括脑组织发育迟缓、轴突再生能力障碍、记忆力改变以及干细胞更新和分化紊乱等。近年来的研究还发现,m6A修饰及其相关蛋白在阿尔茨海默症、帕金森症、脆性X染色体综合征、抑郁症和胶质母细胞瘤等众多神经系统疾病的发展进程中扮演关键角色。本文主要综述了近年来在中枢神经系统中m6A修饰调控机制研究的相关进展,重点介绍了m6A修饰介导的基因表达调控对中枢神经系统生物学功能以及多种相关疾病的影响,以期为中枢神经系统疾病提供新的研究靶点和治疗方向。

Soil restoration research advances of artificial sand-binding vegetation ecosystem in the Tengger Desert, Northern China

Soil plays an important role in desert ecosystem, and is vital in constructing a steady desert ecosystem. The management and restoration of desertified land have been the focus of much discussion. The soil in Shapotou desert region has developed remarkably since artificial sand-binding vegetation established in 1946. The longer the period of dune stabilization, the greater the thickness of microbiotic crusts and subsoil. Meanwhile, proportion of silt and clay increased significantly, and soil bulk density declinced. The content of soil organic matter, N, P, and K similarly increased. Therefore, soil has developed from aeolian sand soil to Calcic-Orthic aridisols. This paper discusses the effects brought about by dust, microbiotic soil crust and soil microbes on soil-forming process. Then, we analyzed the relation between soil formation and sand-binding vegetation evolution, in order to provide a baseline for both research on desert ecosystem recovery and ecological environment governance in arid and semi-arid areas.

CEPC Technical Design Report

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.

Discovery of β-nitrostyrene derivatives as potential quorum sensing inhibitors for biofilm inhibition and antivirulence factor therapeutics against Serratia marcescens

Quorum sensing(Qs)inhibition has emerged as a promising target for directed drug design,providing an appealing strategy for developing antimicrobials,particularly against infections caused by drug-resistant pathogens.In this study,we designed and synthesized a total of 33β-nitrostyrene derivatives using 1-nitro-2-phenylethane(NPe)as the lead compound,to target the facultative anaerobic bacterial pathogen Serratia marcescens.The QS-inhibitory effects of these compounds were evaluated using S.marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026.Among the 33 newβ-nitrostyrene derivatives,(E)-1-methyl-4-(2-nitrovinyl)benzene(m-NPe,compound 28)was proven to be a potent inhibitor that reduced biofilm formation of S.marcescens NJ01 by 79%.Scanning electron microscopy(SEM)and confocal laser scanning microscopy(CLSM)results revealed that treatment with m-NPe(50μg/ml)not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%.m-NPe(50μg/ml)decreased virulence factors in S.marcescens NJ01,reducing the activity of protease,prodigiosin,and extracellular polysaccharide(EPs)by 36%,72%,and 52%,respectively.In S.marcescens 4547,the activities of hemolysin and EPs were reduced by 28%and 40%,respectively,outperforming the positive control,vanillic acid(VAN).The study also found that the expression levels of QS-and biofilm-related genes(flhD,fimA,fimC,sodB,bsmB,pigA,pigC,and shlA)were downregulated by 1.21-to 2.32-fold.Molecular dynamics analysis showed that m-NPe could bind stably to SmaR,Rhll,RhiR,LasR,and CviR proteins in a 0.1 M sodium chloride solution.Importantly,a microscale thermophoresis(MST)test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor(QSl)against S.marcescens.Overall,this study highlights the efficacy of m-NPe in suppressing the virulence factors of S.marcescens,identifying it as a new potential Qsl and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.

Inhibition of ROS elevation and damage to mitochondrial function prevents lead-induced neurotoxic effects on structures and functions of AFD neurons in Caenorhabditis elegans

Here we investigated the possible roles of oxidative stress in the formation of decreased thermotaxis to cultivation temperature in lead （Pb）-exposed nematodes Caenorhabditis elagans. Exposure to Pb at the examined concentrations decreased thermotaxis behaviors, and induced severe deficits in the structural properties of AFD sensory neurons. Meanwhile, Pb exposure caused the induction of severe oxidative damage, reactive oxygen species （ROS） production, and mitochondrial dysfunction in young adults. Moreover, pre-treatment with the antioxidants dimethyl sulfoxide （DMSO）, ascorbate and N-acetyl-L-cysteine （NAC）, used to inhibit both the ROS elevation and the mitochondrial dysfunction caused by Pb exposure, at the L2-1arval stage prevented the induction of oxidative damage and the formation of severe deficits in thermotaxis and structural properties of AFD sensory neurons in Pb-exposed young adults. Therefore, the formation of oxidative stress caused by Pb exposure may be due to both the induction of ROS elevation and damage to mitochondrial function, and oxidative stress may play a key role in inducing the neurotoxic effects on the structures and function of AFD sensory neurons in Pb-exposed nematodes.

Effect of graphene oxide exposure on intestinal Wnt signaling in nematode Caenorhabditis elegans

Exposure to engineered nanomaterials(ENMs), such as graphene oxide(GO), can potentially induce the response of various molecular signaling pathways, which can mediate the protective function or the toxicity induction.Wnt signaling pathway is conserved evolutionarily in organisms.Using Caenorhabditis elegans as an in vivo assay model, we investigated the effect of GO exposure on intestinal Wnt signaling.In the intestine, GO exposure dysregulated Frizzled receptor MOM-5, Disheveled protein DSH-2, GSK-3(a component of APC complex), and two β-catenin proteins(BAR-1 and HMP-2), which mediated the induction of GO toxicity.In GO exposed nematodes, a Hox protein EGL-5 acted as a downstream target of BAR-1, and fatty acid transport ACS-22 acted as a downstream target of HMP-2.Functional analysis on HMP-2 and ACS-22 suggested that the dysregulation of these two proteins provides an important basis for the observed deficit in functional state of intestinal barrier.Our results imply the association of dysregulation in physiological and functional states of intestinal barrier with toxicity induction of GO in organisms.

Molecular genetic studies of familial Meniere’s disease

Dear Editor.Meniere's disease(MD,MIM 156000),a chronic clinical illness affecting the inner ear,presents as episodes of spontaneous vertigo,fluctuating sensorineural hearing loss,tinnitus,and aural fullness.Endolymphatic hydrops in the cochlear duct and vestibular organs is considered the underlying histopathologic characteristic of MD.Most MD cases are sporadic(sporadic Meniere's disease,SMD),and approximately 4%-20%of patients with MD have a familial history.

Lensless Fourier-transform terahertz digital holography for real-time full-field phase imaging

With the development of continuous-wave terahertz(THz) sources and array detectors, the pursuit of highfidelity real-time imaging is receiving significant attention within the THz community. Here, we report a real-time full-field THz phase imaging approach based on lensless Fourier-transform THz digital holography.A triangular interferometric layout is proposed based on an oblique illumination of 2.52 THz radiation, which is different from other lensless holographic configurations at other frequencies. A spherical reference beam is generated by a reflective parabolic mirror with minor propagation loss. The complex-valued images are reconstructed using a single inverse Fourier transform of the hologram without complex calculation of the diffraction propagation. The experimental result for a Siemens star validates the lateral resolution of-46 μm in the diagonal direction. Sub-pixel image registration and image stitching algorithms are applied to enlarge the area of the reconstructed images. The dehydration process of an aquatic plant leaf(Hottonia inflata) is monitored for the first time, to the best of our knowledge, at the THz band. Rapid variations in water content and morphology are measured with a time interval of 0.6 s and a total time of 5 min from a series of reconstructed amplitude and phase images, respectively. The proposed method has the potential to become a powerful tool to investigate spontaneous phenomena at the THz band.

Continuous-wave terahertz diffraction tomography for measuring three-dimensional refractive index maps

Three-dimensional(3D)refractive index(RI)distribution is important to reveal the object’s inner structure.We implemented terahertz(THz)diffraction tomography with a continuous-wave single-frequency THz source for measuring 3D RI maps.The off-axis holographic interference configuration was employed to obtain the quantitative scattered field of the object under each rotation angle.The 3D reconstruction algorithm adopted the filtered backpropagation method,which can theoretically calculate the exact scattering potential from the measured scattered field.Based on the Rytov approximation,the 3D RI distribution of polystyrene foam spheres was achieved with high fidelity,which verified the feasibility of the proposed method.

Continuous-wave terahertz in-line holographic diffraction tomography with the scattering fields reconstructed by a physics-enhanced deep neural network

Diffraction tomography is a promising,quantitative,and nondestructive three-dimensional(3D)imaging method that enables us to obtain the complex refractive index distribution of a sample.The acquisition of the scattered fields under the different illumination angles is a key issue,where the complex scattered fields need to be retrieved.Presently,in order to develop terahertz(THz)diffraction tomography,the advanced acquisition of the scattered fields is desired.In this paper,a THz in-line digital holographic diffraction tomography(THz-IDHDT)is proposed with an extremely compact optical configuration and implemented for the first time,to the best of our knowledge.A learning-based phase retrieval algorithm by combining the physical model and the convolution neural networks,named the physics-enhanced deep neural network(PhysenNet),is applied to reconstruct the THz in-line digital hologram,and obtain the complex amplitude distribution of the sample with high fidelity.The advantages of the PhysenNet are that there is no need for pretraining by using a large set of labeled data,and it can also work for thick samples.Experimentally with a continuous-wave THz laser,the PhysenNet is first demonstrated by using the thin samples and exhibits superiority in terms of imaging quality.More importantly,with regard to the thick samples,PhysenNet still works well,and can offer 2D complex scattered fields for diffraction tomography.Furthermore,the 3D refractive index maps of two types of foam sphere samples are successfully reconstructed by the proposed method.For a single foam sphere,the relative error of the average refractive index value is only 0.17%,compared to the commercial THz time-domain spectroscopy system.This demonstrates the feasibility and high accuracy of the THz-IDHDT,and the idea can be applied to other wavebands as well.

Precision Higgs physics at the CEPC

The discovery of the Higgs boson with its mass around 125 GeV by the ATLAS and CMS Collaborations marked the beginning of a new era in high energy physics.The Higgs boson will be the subject of extensive studies of the ongoing LHC program.At the same time,lepton collider based Higgs factories have been proposed as a possible next step beyond the LHC,with its main goal to precisely measure the properties of the Higgs boson and probe potential new physics associated with the Higgs boson.The Circular Electron Positron Collider(CEPC)is one of such proposed Higgs factories.The CEPC is an e^+e^- circular collider proposed by and to be hosted in China.Located in a tunnel of approximately 100 km in circumference,it will operate at a center-of-mass energy of 240 GeV as the Higgs factory.In this paper,we present the first estimates on the precision of the Higgs boson property measurements achievable at the CEPC and discuss implications of these measurements.

Primary observations of the existence of Fas-like cytoplasmic death factor in plant cells

The main activity of Fas is to trigger cytoplasm death program in animal cells. In G2 pea, vacuole plays a pivotal role in inducing cell death in the cytoplasm of long-day (LD) grown apical meristem cells. Expression patterns of the Fas in G2 pea cells revealed that the Fas is mainly localized in the vacuole of cells undergoing programmed cell death (PCD). The Fas expression is corresponding to the initiation of menadione-induced PCD in tobacco protoplasts. The results suggest the existence of the Fas-like mediated cytoplasmic death pathway in plant cells.

NPR-9 regulates the innate immune response in Caenorhabditis elegans by antagonizing the activity of AIB interneurons

npr-9 encodes a homologue of the gastrin-releasing peptide receptor (GRPR) and is expressed in AIB interneurons. In this study, we investigated the role of NPR-9 in the neuronal control of innate immunity using the model system Caenorhabditis elegans. After exposure to Pseudomonas aeruginosa PA14, npr-9(tm1652) mutants showed resistance to infection, decreased PA14 colonization and increased expression of immunity-related genes. Nematodes overexpressing NPR-9 exhibited increased susceptibility to infection, increased PA14 colonization and reduced expression of immunity-related genes. In nematodes, ChR2-mediated AIB interneuron activation strengthened the innate immune response and decreased PA14 colonization. Overexpression of NPR-9 suppressed the innate immune response and increased PA14 colonization in nematodes with the activation of AIB interneurons mediated by ChR2 or by expressing pkc-1(gf) in AIB interneurons. We, therefore, hypothesize that NPR-9 regulates the innate immune response by antagonizing the activity of AIB interneurons. Furthermore, expression of GRPR, the human homologue of NPR-9, could largely mimic NPR-9 function by regulating innate immunity in nematodes. Our results provide insight into the pivotal role of interneurons in controlling innate immunity and the complex biological functions of GRPRs.

Understanding auditory neuropathy spectrum disorder： a system- atic review in transgenic mouse models

Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mechanism underlying this disorder is not clear. We therefore performed a systematic review of genetic mouse models with different gene mutations to provide a valuable tool for better understanding of the process and the possible molecular mechanisms. Of the 18 articles retrieved, nine met the required criteria. All biochemical, histological, and electrophysiological results were recorded for each of the mouse models, as was the transgenic technology. This review provides a summary of different mouse models that may play an important role in the diagnosis and management of auditory neuropathy spectrum disorder in the future.

A novel de novo mutation of ACTG1 in two sporadic non-syndromic hearing loss cases

Dear Editor,Actins are a family of essential cytoskeletal proteins involved in nearly all cellular processes（Lambrechts et al.,2004）.Of the six human genes that encode actins,only ACTG1and ACTB are ubiquitously expressed.ACTG1（OMIM#604717）,which is linked to the DFNA20/26 locus,wasidentified in autosomal dominant, non-syndromic hearing loss （NSHL） cases （Baek et al., 2012; Liu et al., 2008; Park et al., 2013; Yuan et al., 2016）. In addition, some ACTG1 （OMIM #614583） mutations are associated with Baraitser-Winter syndrome, which is characterized by developmental delay, facial dysmorphologies, brain malformations, colobomas, and variable hearing loss （Riviere et al., 2012）.

Administration with Bushenkangshuai Tang alleviates UV irradiation- and oxidative stress-induced lifespan defects in nematode Caenorhabditis elegans

During normal metabolism,oxidative bypro-ducts will inevitably generate and damage molecules thereby impairing their biological functions,including the aging process.Bushenkangshuai Tang(补肾抗衰方,BT)is a traditional Chinese medicine widely used for clini-cally treating premature ovarian failure.In the present study,BT administration at high concentrations signifi-cantly increased lifespan,slowed aging-related decline,and delayed accumulation of aging-related cellular damage in wild-type Caenorhabditis elegans.BT admin-istration could further largely alleviate the aging defects induced by UV and oxidative stresses,and BT administra-tion at different concentrations could largely rescue the aging defects in mev-1 mutant animals.The protective effects of BT administration on aging process were at least partially dependent on the Ins/IGF-like signaling pathway.Moreover,BT administration at different concentrations obviously altered the expression patterns of antioxidant genes and suppressed the severe stress responses induced by UV and oxidative stresses,suggesting that BT-induced tolerance to UV or oxidative stress might result from reactive oxygen species scavenging.BT administration during development was not necessarily a requirement for UV and oxidative stress resistance,and the concentrations of administrated BT examined were not toxic for nematodes.Therefore,BT administration could effectively retrieve the aging defects induced by UV irradiation and oxidative stress in Caenorhabditis elegans.

Binary diffractive lens with subwavelength focusing for terahertz imaging

The converging lens is one of the key components in high-resolution terahertz imaging.In this Letter,a binary diffractive lens is proposed for the scanning imaging system working at 278.6 GHz,in which a convergent beam with a waist diameter of0.65 mm is generated,and 1 mm lateral imaging resolution is realized.This low-cost terahertz lens,constituted by concentric rings with different radii,is optimized by stimulated annealing algorithm and fabricated by three-dimensional printing.Compared with the conventional transmissive convex lens,higher resolution and enhanced imaging quality are achieved via smaller focal spot of the illumination beam.This type of lens would promote terahertz imaging closer to practical applications such as nondestructive testing and other scenarios.

Simulation study of the performance of quadruple-GEM detectors

Background Gas Electron Multiplier(GEM)detectors are widely used for high-energy physics experiments,such as the triple-GEM detector installed in CMS,due to their excellent performance.A quadruple-GEM detector is regarded as the candidate for the upgrade projects of the High Luminosity LHC(HL-LHC).Method In this paper,key performance characteristics of quadruple-GEM detectors are studied in detail based on Monte Carlo simulation using the Garfield++and ANSYS software packages.The parameterization method is adopted.Result The spatial and time resolution,effective gain,efficiency,and electron transparency are obtained via simulation for different detector geometries and operating conditions.We create a quadruple-GEM structure that meets the geometric requirements of the CMS endcap muon detectors.Conclusion These studies help to understand the physical mechanisms of GEM detectors and provide references for the detector design,operating condition optimization and technical scheme selection in future applications.