Task-Oriented Topology System Synthesis of Reconfigurable Legged Mobile Lander Integrating Active and Passive Metamorphoses

To explore hostile extraterrestrial landforms and construct an engineering prototype,this paper presents the task-oriented topology system synthesis of reconfigurable legged mobile lander(ReLML)with three operation modes from adjusting,landing,to roving.Compared with our preceding works,the adjusting mode with three rotations(3R)provides a totally novel exploration approach to geometrically matching and securely arriving at complex terrains dangerous to visit currently;the landing mode is redefined by two rotations one translation(2R1T),identical with the tried-and-tested Apollo and Chang'E landers to enhance survivability via reasonable touchdown buffering motion;roving mode also utilizes 2R1T motion for good motion and force properties.The reconfigurable mechanism theory is first brought into synthesizing legged mobile lander integrating active and passive metamorphoses,composed of two types of metamorphic joints and metamorphic execution and transmission mechanisms.To reveal metamorphic principles with multiple finite motions,the finite screw theory is developed to present the procedure from unified mathematical representation,modes and source phase derivations,metamorphic joint and limb design,to final structure assembly.To identify the prototype topology,the 3D optimal selection matrix method is proposed considering three operation modes,five evaluation criteria,and two topological subsystems.Finally,simulation verifies the whole task implementation process to ensure the reasonability of design.

Identification of SARS-CoV-2-against aptamer with high neutralization activity by blocking the RBD domain of spike protein 1

Dear Editor,The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)poses a great threat to the public health of people and the normal economic and social development around the world.As of January 8,2021,more than 88 million people were infected with SARS-CoV-2,resulting in more than 1.9 million death.

siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment

Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug delivery.Herein,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the siRNA.Surprisingly,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane structure.Resorting to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.

Nanoliposome-encapsulated caged-GABA for modulating neural electrophysiological activity with simultaneous detection by microelectrode arrays

Effective and precise neural modulation with real-time detection in the brain is of great importance and represents a significant challenge.Nanoliposome-encapsulated light-sensitive compounds have excellent characteristics such as high temporal and spatial resolution,delayed drug clearance,and restricted drug biodistribution for neural modulation.In this study,we developed a nanoliposome-based delivery system for ruthenium-based caged GABA compounds(Nanolipo-Ru)to modulate neural activity and allow for real-time monitoring using the microelectrode arrays(MEAs).The Nanolipo-Ru nanoparticles had an average size of 134.10±4.30 nm and exhibited excellent stability for seven weeks.For the in vivo experiment in the rat,release of GABA by Nanolipo-Ru under blue light illumination resulted in an average firing rate reduction in interneurons and pyramidal neurons in the same brain region of 79.4%and 81.6%,respectively.Simultaneously,the average power of local field potentials in the 0–15 Hz range degraded from 4.34 to 0.85 mW.In addition,the Nanolipo-Ru nanoparticles have the potential to provide more flexible timing of modulation than unencapsulated RuBi-GABA in the experiments.These results indicated that Nanolipo-Ru could be an effective platform for regulating neuronal electrophysiology.Furthermore,nanoliposomes with appropriate modifications would render promising utilities for targeting of specific types of neurons in the future.

基于血清学指标的联合模型诊断代偿期肝硬化轻微型肝性脑病的价值

目的探讨血清学指标对代偿期肝硬化轻微型肝性脑病(MHE)的诊断价值,构建基于血清学指标的联合模型并评估其对MHE的诊断价值。方法前瞻性、多中心研究。选取2021年10月至2022年8月来自我国15个省(自治区、直辖市)的23家医院就诊的代偿期肝硬化患者263例。收集患者临床资料及实验室检查结果,并计算终末期肝病模型(MELD)评分。使用基线血氨测量值/正常参考值上限(AMM-ULN)集中校正各中心血氨测量结果,以我国《肝硬化肝性脑病诊疗指南》标准,数字连接试验-A、数字符号试验均异常作为诊断MHE的标准。基于R语言caret包将患者随机(7∶3)分为训练集(n=185)和验证集(n=78)。通过Logistic回归构建诊断MHE的联合模型;受试者工作特征曲线下面积(AUC)、Hosmer-Lemeshow拟合优度检验及校准曲线图评估诊断性能,并用Bootstrap法(n=200)进行内部验证;Delong检验比较AUC之间的差异。结果训练集中,MHE占37.8%(70/185),MHE组AMM-ULN、白蛋白、血小板、碱性磷酸酶、国际标准化比值、终末期肝病模型评分以及教育年限与无MHE组比较,差异有统计学意义(P均<0.05)。多因素Logistic回归分析显示,AMM-ULN(OR=1.78,95%CI 1.05~3.14,P=0.038)和MELD评分(OR=1.11,95%CI 1.04~1.20,P=0.002)是MHE的独立危险因素,AUC分别为0.663和0.625。联合AMM-ULN、MELD评分和教育年限的联合模型诊断MHE的AUC为0.755,特异度和敏感度分别为85.2%和55.7%。Hosmer-Lemeshow拟合优度检验表明模型具有较好的校准度(P=0.733),联合模型内部验证AUC为0.752。Delong检验显示联合模型诊断效能优于单独使用血氨(P=0.020)和MELD评分(P=0.003)。验证集中,联合模型诊断MHE的AUC为0.794,Hosmer-Lemeshow拟合优度检验显示有较好的校准度(P=0.841)。结论基于AMM-ULN、MELD评分和教育年限的联合模型可提高对MHE的诊断价值。

CYP2C19 Genotyping Plus Therapeutic Drug Monitoring Dependent Voriconazole Treatment for Invasive Pulmonary Aspergillosis in a Patient with Liver Failure

Invasive pulmonary aspergillosis(IPA)is a lethal infectious disease with high mortality in patients with liver failure.Early recognition of the risk factors prompting earlier diagnosis and treatment may improve the outcomes.Voriconazole is recommended as the first-line drug for IPA,but hepatotoxicity limits its use in the context of liver diseases.We report a case of a 63-year-old female who was admitted to the Third Affiliated Hospital of Hebei Medical University due to IPA after glucocorticoid therapy for liver failure.The polymorphism of cytochrome P450(CYP)isoenzymes showed CYP2C19∗1/∗2 genotype associated with intermediate metabolism of voriconazole.However,the patient developed side effects such as skin rash,vomiting,hyperbilirubinemia,and alteration of consciousness,even if she received half of the recommended dosage for voriconazole.Therapeutic drug monitoring(TDM)was applied to guide the dosage adjustment of voriconazole in this patient,and consequently,the patient presented a favorable outcome.In conclusion,genotyping screening plus TDM dependent individualized treatment of voriconazole may improve the survival of liver failure patient with IPA.

Prevalence and risk factors for minimal hepatic encephalopathy in cirrhotic patients with different etiologies

Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.Methods:This multicenter,cross-sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25,2021,to January 10,2023(Trial registration:https://clinicaltrials.gov/[NCT05140837]).The patients'demographics,etiologies of cirrhosis,and laboratory test results were collected.The psychometric hepatic encephalopathy score(PHES)was determined in all patients to screen for MHE.Multivariate logistic analyses were performed to identify the risk factors for MHE.Results:In total,736 patients with cirrhosis were analyzed.The prevalence of MHE was 42.0%(n=309).The primary etiology among all patients was hepatitis B virus(HBV)-related cirrhosis(71.9%[529/736]).The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis(57.1%[40/70])than in those with HBV-related cirrhosis(40.6%[215/529],p=0.009)or hepatitis C virus(HCV)-related cirrhosis(38.2%[26/68],p=0.026).Age(odds ratio[OR],1.042;95%confidence interval[CI],1.024-1.059;p<0.001),duration of education(OR,0.935;95%CI,0.899-0.971;p=0.001),etiology(OR,1.740;95%CI,1.028-2.945;p=0.039),and high MELD-Na scores(OR,1.038;95%CI,1.009-1.067;p=0.009)were independent risk factors for MHE.When patients with cirrhosis of different etiologies were analyzed separately,the results showed that age(OR,1.035;95%CI,1.014-1.057;p=0.001)and duration of education(OR,0.924;95%CI,0.883-0.966;p=0.001)were risk factors for MHE among patients with HBV-related cirrhosis,whereas age(OR,1.138;95%CI,1.033-1.254;p=0.009)and creatinine concentration(OR,16.487;95%CI,1.113-244.160;p=0.042)were risk factors for MHE in patients with HCV-related cirrhosis.No risk factors for MHE were found in patients with autoimmune cirrhosis.For patients with alcoholic cirrhosis,the platelet count(OR,1.014;95%CI,1.000-1.027;p=0.045)was a risk factor for MHE.The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies.Patients with HBV-related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis(p=0.007 and p<0.001),better on Number Connection Test B than those with HCV-related cirrhosis(p=0.020),and better on the line tracing test than those with autoimmune cirrhosis(p=0.037).Conclusion:The etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE.The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies.Further studies are required to verify these findings.

Launching, perceiving, and diminishing of airborne signals

Aphids are highly destructive pests that greatly hurt the agricultural industry.Transmitting over 40%of plant viruses,they are the most destructive pests that the agricultural industry faces(Gong et al.,2023).Aphids feed on plants,and in doing so,they consume sap from one plant and then move to another and inject their saliva into the new plant(Hooks and Fereres,2006).This cycle causes diseases and viral pathogens to become rampant between plants as the aphids carry viral pathogens from one plant to another and so on.

Increasing importance of ammonia emission abatement in PM_(2.5)pollution control

在新冠肺炎疫情期间,中国采取的管制封锁措施大幅减少了交通和工业排放,但农业排放没有受到影响,甚至有所增加.通过全国大气氨浓度地面监测、实时连续观测和卫星观测等手段,我们发现,新冠肺炎疫情管制措施实施期间中国大气氨浓度大范围显著增加,上升幅度在农村地区最为明显(增加22%),在城市和偏远地区变化不明显;而且,管控期间大气氨浓度上升幅度与2015~2019年相同月份相比更大.基于大气化学模式模拟发现,中国北方大气氨浓度上升主要是由农业氨排放增加所致.随着未来我国二氧化硫和氮氧化物等酸性气体排放控制的强化,农业氨排放的协同减排对于进一步削减大气PM污染、提升空气质量尤为重要.进一步分析表明,疫情期间50%农业氨排放可有效抵消氨浓度上升造成的二次无机气溶胶的形成.

Real-time simultaneous recording of electrophysiological activities and dopamine overflow in the deep brain nuclei of a non-human primate with Parkinson’s disease using nano-based microelectrode arrays

Parkinson’s disease(PD)is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons.The precise mechanisms are still unknown.Since the neuronal communications are inherently electrical and chemical in nature,dual-mode detection of PD-related neuroelectrical and neurochemical information is essential for PD research.Subthalamic nucleus(STN)highfrequency stimulation(HFS)can improve most symptoms of PD patients and decrease the dosage of antiparkinsonian drugs.The mechanism of STN-HFS for PD still remains elusive.In this study,a silicon-based dual-mode microelectrode array(MEA)probe was designed and fabricated,and systematic dual-mode detection methods were established.The recording sites were modified using Pt nanoparticles and Nafion to improve the signal-to-noise(SNR)ratio.To evaluate its applicability to PD research,in vivo electrophysiological and electrochemical detection was performed in normal and hemiparkinsonian models,respectively.Through comparison of the dual-mode signals,we demonstrated the following in a PD monkey:(1)the maximum dopamine concentration in the striatum decreased by 90%;(2)the spike firing frequency increased significantly,especially in the region of the cortex;(3)the spectrogram analysis showed that much power existed in the 0–10 Hz frequency band;and(4)following repeated subthalamic nucleus high-frequency stimulation trials,the level of DA in the striatum increased by 16.5μM,which led to a better elucidation of the mechanism of HFS.The dual-mode MEA probe was demonstrated to be an effective tool for the study of neurological disorders.

Biosafety materials:Ushering in a new era of infectious disease diagnosis and treatment with the CRISPR/Cas system

Despite multiple virus outbreaks over the past decade,including the devastating coronavirus disease 2019(COVID-19)pandemic,the lack of accurate and timely diagnosis and treatment technologies has wreaked havoc on global biosecurity.The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)system has the potential to address these critical needs for tackling infectious diseases to detect viral nucleic acids and inhibit viral replication.This review summarizes how the CRISPR/Cas system is being utilized for the treatment and diagnosis of infectious diseases with the help of biosafety materials and highlights the design principle and in vivo and in vitro efficacy of advanced biosafety materials used to deal with virus attacks.

CONCENTRATIONS AND FLUXES OF DISSOLVED NUTRIENTS IN THE YANGTZE RIVER: LONG-TERM TRENDS AND ECOLOGICAL IMPACTS

Intensifying human activity in the Yangtze River Basin(YRB) has substantially increased nutrient concentrations in the Yangtze River Estuary,leading to degradation of the coastal environment.Analysis of nutrient determinations published over the past 50 years reveals a gradual decreasing trend in the concentrations and fluxes of dissolved silicate(DSi).However,both dissolved inorganic nitrogen(DIN) and dissolved inorganic phosphate(DIP) concentrations have increased significantly since the 1970 s.The frequency and area covered by red tide outbreaks have increased greatly during this period,mainly due to changes in nutrient supply ratios [i.e.,N/P(DIN/DIP),N/Si(DIN/DSi),P/Si(DIP/DSi)].A strong correlation was found between the riverine DIN fluxes and the estimated DIN inputs from the major N sources,particularly fertilizers and atmospheric deposition.The data provide a comprehensive assessment of nutrients in the YRB and their ecological impacts and indicate a potentially significant influence of atmospheric deposition on DIN loadings and fluxes.