Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Characteristics study on the oscillation onset and damping of a traveling-wave thermoacoustic prime mover

This paper focuses on the temperature and pressure characteristics of a Swift-Backhaus type traveling-wave thermoacoustic prime mover during its onset and damping processes,in order to understand the intrinsic mechanism of thermoacoustic oscillation onset and the feasibility of using low-grade thermal energy based on a low onset temperature. The influences of heat input and filling pressure on hysteretic loop,due to the noncoincidence between onset and damping processes,are measured and analyzed. The condition for the occurrence of hysteresis is also briefly discussed.

Bubble counter based on photoelectric technique for leakage detection of cryogenic valves

In order to overcome the inconvenience of manual bubble counting, a bubble counter based on photoelectric technique aiming for automatically detecting and measuring minute gas leakage of cryogenic valves is proposed. Experiments have been conducted on a self-built apparatus, testing the performance with different gas inlet strategies (bottom gas-inlet strategy and side gas-inlet strategy) and the influence of gas pipe length (0, 1, 2, 4, 6, 8, 10 m) and leakage rate (around 10, 20, 30, 40 bubbles/min) on first bubble time and bubble rate. A buffer of 110 cm3 is inserted between leakage source and gas pipe to simulate the down- stream cavum adjacent to the valve clack. Based on analyzing the experimental data, experiential parameters have also been summarized to guide leakage detection and measurement for engineering applications. A practical system has already been suc- cessfully applied in a cryogenic testing apparatus for cryogenic valves.

Multidimensional diversity of bird communities across spatial variation of land cover in Zoige on the eastern Qinghai-Tibetan Plateau

Background:Spatial variation of land cover can result in the changes of community similarities and biotic homog-enization,whereby the increasing similarity would reduce the adaptive capacity of biotic assemblages to further disturbance,and degenerate ecosystem services they offer.However,it remains scarce to integrate multidimensional diversity for unveiling how variations in land cover may influence the patterns and processes of biotic homogeniza-tion in the Anthropocene.In this study,we examined how spatial variation of land cover could alter taxonomic,phy-logenetic and functional homogenization of bird communities simultaneously in a compound ecosystem of Zoige Marsh on the eastern Qinghai-Tibetan Plateau.Acting as the largest alpine marsh and peatland in the world,Zoige Marsh has undergone great changes in the land cover pattern due to climate change and anthropogenic activities.Methods:We conducted transect surveys for bird communities over six years(2014‒2019)during breeding sea-sons in four main land cover types(meadow,woodland,village and marsh),representing the spatial variation of land covers in the study area.We compared multidimensional diversity(taxonomic,phylogenetic and functional diver-sity)among land covers to assess the effects of spatial variation in land cover type on bird communities,particularly whether this variation has homogenized biotic communities.Results:Bird communities during breeding seasons were different and complementary in the four land covers.Taxonomic,phylogenetic and functional similarities were significantly lower in meadow than in the other three types,i.e.woodland,village and marsh.However,when we controlled for the effects of taxonomic similarities,the pattern of phylogenetic similarities almost reversed,with the highest standardized effect size(SES)phylogenetic similarity in meadow;and we found no significant difference in SES functional similarity among land covers.Conclusions:Our results suggest that spatial variation of land cover can play a crucial role in regulating multiple dimensions of bird diversity in Zoige Marsh.The findings indicate that taxonomic,phylogenetic and functional homogenization of bird communities may differently response to the variation of land covers.It thus highlights not only the relative roles of different land covers in maintaining biodiversity and community structures of birds,but also the urgency of retarding ecosystem degradations on the eastern Qinghai-Tibetan Plateau.

Synthesis and Luminescence Properties of(Y, Gd)(P, V)O_4:Eu^(3+), Bi^(3+) Red Nano-phosphors with Enhanced Photoluminescence by Bi^(3+), Gd^(3+) Doping

A series of(Y_(1-y), Gdy)_(0.95-x)(P_y, V_(1-y))O_4 :0.05Eu^(3+), xBi^(3+)+phosphors have been successfully prepared by a subsection method. The crystal structure, surface morphology and luminescence properties were investigated. It was found that the sintered samples crystallized in a tetragonal crystal system with space group I_(41)/amd(a = b = 0.7119 nm, c = 0.6290 nm). The products presented rod-like morphology with length of 100-150 nm and width of 50-100 nm. A maximum peak at 619 nm(~5D_0 →~7F_2) was observed in emission spectrum of the phosphors. It was also found that co-doping of Bi^(3+)+, P5+and Gd^(3+)ions into YVO_4:Eu^(3+)can not only made the right edge of the excitation band shift to the long-wavelength region, but also increased the emission intensity at 619 nm sharply and decreased the lifetime of fluorescence decay. These results may expand the application scope of the phosphors.

Impact of load impedance on the performance of a thermoacoustic system employing acoustic pressure amplifier

An acoustic pressure amplifier (APA) is capable of improving the match between a thermoacoustic engine and a load by elevating pressure ratio and acoustic power output. A standing-wave thermoacoustic engine driving a resistance- and-compliance (RC) load through an APA was simulated with linear thermoacoustics to study the impact of load impedance on the performance of the thermoacoustic system. Based on the simulation results, analysis focuses on the distribution of pressure amplitude and velocity amplitude in APA with an RC load of diverse acoustic resistances and compliance impedances. Variation of operating parameters, including pressure ratio, acoustic power, hot end temperature of stack, etc., versus impedance of the RC load is presented and analyzed according to the abovementioned distribution. A verifying experiment has been performed, which indicates that the simulation can roughly predict the system operation in the fundamental-frequency mode.

Macrophages’M1 or M2 by tumor microparticles:lysosome makes decision

Cells deliver messages to their surroundings or distant cells by secreting signaling molecules or releasing extracellular microvesicles(EVs)[1,2].Two types of EVs have been identified:exosomes and microparticles(MPs),which are also termed microvesicles(MVs).Exosomes are endosome-derived EVs(30-100 nm)that deliver information about proteins,mRNAs,and microRNAs to recipient cells[3].MPs are plasma membrane-derived shedding vesicles with sizes ranging from 0.1 to 1μm[4].

Trophic niche and adaptation in highland lizards:sex has greater influences than species matching

The plateau environments are typically arid,cool,and high altitude,posing formidable challenges to wildlife survival due to resource scarcity and harsh conditions.Unraveling ecological adaptability in severe conditions requires a deeper understanding of the niche characteristics of plateau species.Trophic niche,which is a comprehensive indicator describing the energy acquisition strategy of animals,remains relatively understudied in plateau species.Here,by combining stable isotopes and morphological data,we quantified the trophic niches of two allopatric lizard species(Phrynocephalus vlangalii and P.erythrurus)that live in the hinterland of the Qinghai–Tibetan Plateau,and explored how their trophic niches correlate with morphological and environmental factors.While both trophic niche and morphological traits were similar between species,noteworthy distinctions were observed between male and female Phrynocephalus lizards.The morphological traits associated with predation(i.e.limb length and head size)and reproduction(i.e.abdomen length),annual mean temperature,and sex played influential roles in shifting trophic niches.These results imply that sexual dimorphism may facilitate inter-sex divergence in resource utilization,leading to trophic niche variations in the highland lizards.Furthermore,extreme environmental stress can constrain interspecific divergence in morphological and trophic traits.Our findings illustrate the dynamic variations of trophic niches in highland lizards,contributing to a more comprehensive understanding of the adaptation strategies employed by lizard species in plateau environments.

Multi-objective evolutionary optimization for hardware-aware neural network pruning

Neural network pruning is a popular approach to reducing the computational complexity of deep neural networks.In recent years,as growing evidence shows that conventional network pruning methods employ inappropriate proxy metrics,and as new types of hardware become increasingly available,hardware-aware network pruning that incorporates hardware characteristics in the loop of network pruning has gained growing attention,Both network accuracy and hardware efficiency(latency,memory consumption,etc.)are critical objectives to the success of network pruning,but the conflict between the multiple objectives makes it impossible to find a single optimal solution.Previous studies mostly convert the hardware-aware network pruning to optimization problems with a single objective.In this paper,we propose to solve the hardware-aware network pruning problem with Multi-Objective Evolutionary Algorithms(MOEAs).Specifically,we formulate the problem as a multi-objective optimization problem,and propose a novel memetic MOEA,namely HAMP,that combines an efficient portfoliobased selection and a surrogate-assisted local search,to solve it.Empirical studies demonstrate the potential of MOEAs in providing simultaneously a set of alternative solutions and the superiority of HAMP compared to the state-of-the-art hardware-aware network pruning method.

Author correction to“Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry”[Acta Pharmaceutica Sinica B 10(2020)789-798]

The authors regret that there is an error in Fig.2B(Page 793),in which the fluorescence image of the“DMSO(Before&during low pH treatment)”group was mistakenly pasted in the process of assembling figures.This correction does not significantly impact the findings and conclusions of the paper.The authors would like to assure readers that the corrected image does not alter the validity of the research.The original data of these figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.

福建省两栖、爬行动物更新名录

区域物种编目及适时更新是生物多样性研究和保护实践的必要前提。本文基于福建省全省网格化的野外调查,并整合文献资料(截至2021年12月),更新了该省现生本土两栖、爬行动物名录。本名录共收录两栖动物2目9科29属55种、爬行动物2目25科72属126种。其中,分别有4种两栖动物和2种爬行动物是福建省特有种;24种两栖动物和18种爬行动物的模式产地位于福建省。与《福建省两栖动物区系及地理区划》和《福建省爬行动物区系及地理区划》的物种名录相比,本名录新增物种22种,删除8个物种,修订64个物种的名称。有6种爬行动物被列为国家I级重点保护动物,分别有5种两栖动物和25种爬行动物被列为II级保护动物。10种两栖动物被《中国生物多样性红色名录•脊椎动物(第四卷):两栖动物》评估为受胁物种(2种极危,1种濒危,7种易危,分别占两栖动物物种数的3.64%、1.82%和12.73%);41种爬行动物被《中国生物多样性红色名录•脊椎动物(第三卷):爬行动物》评估为受胁物种(11种极危,15种濒危,15种易危,分别占物种数的8.73%、11.90%和11.90%)。

A novel nonviral nanoparticle gene vector: Poly-L-lysine- silica nanoparticles

DNA delivery is a core technology for gene structure and function research as well as clinical settings. The ability to safely and efficiently targeted transfer foreign DNA into cells is a fundamental goal in biotechnology. With the development of nanobiotechnology, nanoparticle gene vectors brought about new hope to reach the goal. In our research, silica nanoparticles (SiNP) were synthesized first in a microemulsion system polyoxyethylene nonylphenyl ether (OP-10)/cyclohexane/ammonium hydroxide, at the same time the effects of SiNP size and its distribution were elucidated by orthogonal analysis; then poly-L-lysine (PLL) was linked on the surface of SiNP by nanoparticle surface energy and electrostatically binding; lastly a novel complex nanomate-rial-poly-L-lysine-silica nanoparticles (PLL-SiNP) wasprepared. The analysis of plasmid DNA binding and DNase I enzymatic degradation discovered that PLL-SiNP could bind DNA, and protect it against enzymatic degradation. Cell transfection showed that

Establishment of pseudovirus infection mouse models for in vivo pharmacodynamics evaluation of filovirus entry inhibitors

Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4(BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and drugs.An HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here,we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro. The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.

Evolutionary Optimization: Pitfalls and Booby Traps

Evolutionary computation （EC）, a collective name rithms, is one of the fastest-growing areas in computer science. for a range of metaheuristic black-box optimization algo- Many manuals and ＂how-to＇s on the use of different EC methods as well as a variety of free or commercial software libraries are widely available nowadays. However, when one of these methods is applied to a real-world task, there can be many pitfalls and booby traps lurking certain aspects of the optimization problem that may lead to unsatisfactory results even if the algorithm appears to be correctly implemented and executed, These include the convergence issues, ruggedness, deceptiveness, and neutrality in the fitness landscape, epistasis, non-separability, noise leading to the need for robustness, as well as dimensionality and scalability issues, among others. In this article, we systematically discuss these related hindrances and present some possible remedies. The goal is to equip practitioners and researchers alike with a clear picture and understanding of what kind of problems can render EC applications unsuccessful and how to avoid them from the start.

Measurement of boiling heat transfer coefficient in liquid nitrogen bath by inverse heat conduction method

Inverse heat conduction method (IHCM) is one of the most effective approaches to obtaining the boiling heat transfer coefficient from measured results. This paper focuses on its application in cryogenic boiling heat transfer. Experiments were conducted on the heat transfer of a stainless steel block in a liquid nitrogen bath, with the assumption of a 1D conduction condition to realize fast acquisition of the temperature of the test points inside the block. With the inverse-heat conduction theory and the explicit finite difference model, a solving program was developed to calculate the heat flux and the boiling heat transfer coefficient of a stainless steel block in liquid nitrogen bath based on the temperature acquisition data. Considering the oscillating data and some unsmooth transition points in the inverse-heat-conduction calculation result of the heat-transfer coefficient, a two-step data-fitting procedure was proposed to obtain the expression for the boiling heat transfer coefficients. The coefficient was then verified for accuracy by a comparison between the simulation results using this expression and the verifying experimental results of a stainless steel block. The maximum error with a revised segment fitting is around 6%, which verifies the feasibility of using IHCM to measure the boiling heat transfer coefficient in liquid nitrogen bath.

Evolutionary Computation for Large-scale Multi-objective Optimization: A Decade of Progresses

Large-scale multi-objective optimization problems(MOPs)that involve a large number of decision variables,have emerged from many real-world applications.While evolutionary algorithms(EAs)have been widely acknowledged as a mainstream method for MOPs,most research progress and successful applications of EAs have been restricted to MOPs with small-scale decision variables.More recently,it has been reported that traditional multi-objective EAs(MOEAs)suffer severe deterioration with the increase of decision variables.As a result,and motivated by the emergence of real-world large-scale MOPs,investigation of MOEAs in this aspect has attracted much more attention in the past decade.This paper reviews the progress of evolutionary computation for large-scale multi-objective optimization from two angles.From the key difficulties of the large-scale MOPs,the scalability analysis is discussed by focusing on the performance of existing MOEAs and the challenges induced by the increase of the number of decision variables.From the perspective of methodology,the large-scale MOEAs are categorized into three classes and introduced respectively:divide and conquer based,dimensionality reduction based and enhanced search-based approaches.Several future research directions are also discussed.

Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry

The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics.Dietary supplements,especially natural products that are edible and safe for human use,are a good source of drug discovery with potential for uncovering novel applications,In this study,we tested 40 natural products of dietary supplements and identified capsaicin,a common dietary supplement abundant in chili peppers,as an inhibitor of Lassa virus(LASV)entry with EC5,of 6.9-10.0μmol/L using an HIV based pseudo virus platform.Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus(LCMV),showing a preferential activity against LASV.Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide(SSP)-GP2 transmembrane(GP2TM)region of the LASV surface glycoprotein.Mutational study revealed the key residues Ala25,Val431,Phe434 and Val435 in SsP-CP2TM region in capsaicin’s antiviral effect.This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV,providing detailed interaction hot spots in the unique SSP-GP2TMinterface of LASV glycoprotein that is crucial in fusion inhibition,and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.

Parallel exploration via negatively correlated search

Effective exploration is key to a successful search process.The recently proposed negatively correlated search(NCS)tries to achieve this by coordinated parallel exploration,where a set of search processes are driven to be negatively correlated so that different promising areas of the search space can be visited simultaneously.Despite successful applications of NCS,the negatively correlated search behaviors were mostly devised by intuition,while deeper(e.g.,mathematical)understanding is missing.In this paper,a more principled NCS,namely NCNES,is presented,showing that the parallel exploration is equivalent to a process of seeking probabilistic models that both lead to solutions of high quality and are distant from previous obtained probabilistic models.Reinforcement learning,for which exploration is of particular importance,are considered for empirical assessment.The proposed NCNES is applied to directly train a deep convolution network with 1.7 million connection weights for playing Atari games.Empirical results show that the significant advantages of NCNES,especially on games with uncertain and delayed rewards,can be highly owed to the effective parallel exploration ability.

Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1

Macrophages in tumors(tumor-associated macrophages,TAMs),a major population within most tumors,play key homeostatic functions by stimulating angiogenesis,enhancing tumor cell growth,and suppressing antitumor immunity.Resetting TAMs by simple,efficacious and safe approach(s)is highly desirable to enhance antitumor immunity and attenuate tumor cell malignancy.Previously,we used tumor cell-derived microparticles to package chemotherapeutic drugs(drug-MPs),which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments,implicating that drug-MPs might reset TAMs,considering the inhibitory effects of M2 macrophages on neutrophil recruitment and activation.Here,we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-βrelease.Mechanistically,drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases,resulting in superoxide anion formation,which further amplifies lysosomal ROS production and pH value by activating lysosomal NOX2.Consequently,lysosomal Ca^(2+)signaling is activated,thus polarizing macrophages towards M1.Meanwhile,the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-βproduction.This lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity.These findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of macrophages.This mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade.

应用于低温流体流量计的多孔板性能数值研究（英文）

目的:相较于常温流体,低温流体的物性存在显著不同,因而对流量计的工作特性也会带来相应的影响。本文旨在探讨多孔板应用于低温流体流量测量时的性能(即流出系数与压力损失系数)特征。创新点:基于数值研究结果,发现多孔板流量计应用于低温流体流量测量时,其稳定测量区间上限雷诺数显著增大,并基于物性特点从空化特性的角度探讨上限雷诺数显著增大的原因。方法:采用数值模拟的方法,经网格独立性验证(表1和图5)和模型验证(图6和图8)后,结合Realizableκ-ε湍流模型与Schnerr–Sauer空化模型,研究同一种结构的多孔板应用于液氮、液氧、液氢三种低温流体和水流量测量时其流出系数与压力损失系数变化的异同(图11、图12和表5);并基于低温流体的物性特点(表3),对其具有较大上限雷诺数的计算结果进行原因分析。结论:对于同一种多孔板结构,与水相比,低温流体具有较宽的稳定雷诺数测量范围,其中,与多孔板结构相关的下限雷诺数差异较小,而受空化影响的上限雷诺数差别较大;低温流体具有较大的上限雷诺数,其原因在于,与水相比较,低温流体的密度与运动粘度平方的乘积?v2明显较小。