Pressure-induced structural,electronic,and superconducting phase transitions in TaSe_(3)

TaSe_(3)has garnered significant research interests due to its unique quasi-one-dimensional crystal structure,which gives rise to distinctive properties.Using crystal structure search and first-principles calculations,we systematically investigated the pressure-induced structural and electronic phase transitions of quasi-one-dimensional TaSe_(3)up to 100 GPa.In addition to the ambient pressure phase(P2_(1)/m-I),we identified three high-pressure phases:P2_(1)/m-II,Pnma,and Pmma.For the P2_(1)/m-I phase,the inclusion of spin-orbit coupling(SOC)results in significant SOC splitting and changes in the band inversion characteristics.Furthermore,band structure calculations for the three high-pressure phases indicate metallic natures,and the electron localization function suggests ionic bonding between Ta and Se atoms.Our electron-phonon coupling calculations reveal a superconducting critical temperature of approximately 6.4 K for the Pmma phase at 100 GPa.This study provides valuable insights into the high-pressure electronic behavior of quasi-one-dimensional TaSe_(3).

目标责任制能否提高政府回应性?——基于保障性住房政策的分析

【问题】目标责任制已作为绩效管理的有效方式被广泛实践。大量研究揭示出目标责任制在强化地方政府的政治激励、改善政策执行力度中的作用,但较少研究关注自上而下的目标考核机制对政府回应性的意义。本研究以保障性住房政策为例,考察目标责任制在强化地方政府政策遵从行为的同时,是否会提高地方政府对当地公众诉求的重视程度及回应性。【方法】本研究以保障性住房政策执行与建设目标考核为例,结合“人民网地方领导留言板”政务大数据与政府工作报告文本数据,构建2010—2015年间全国327个城市的面板数据库,运用多层模型探究目标责任制下的保障性住房政策执行压力对地方政府回应性的影响。【发现】“十二五”期间,保障房建设目标更多、目标责任制压力更大的城市对本地居民住房诉求的回应度并未显著增加;相反,房价收入比较高、住房需求较大的城市,当地官员对公民住房诉求的回应性较低。【贡献】在社会民生类政策领域,目标责任制在促使地方政府主动回应公民诉求方面的作用有限。本研究对完善责任监督制、完善住房保障政策体系有所借鉴和参考。

骨形态发生蛋白信号通路及其交叉对话对下颌骨发育的影响

下颌骨是颅面部唯一能自主活动的骨,可发挥咀嚼、发音和吞咽等多种重要功能。骨形态发生蛋白(BMP)信号通路在骨和软骨的形成及稳态维持中起到重要作用,对下颌骨的发育是不可或缺的。已知BMP信号通路的配体、受体及其下游多种细胞因子与其他信号通路相关联,组成一个复杂且庞大的信号网络,共同调节下颌骨的发育。本文主要介绍BMP信号通路以及与BMP信号通路交叉对话的信号通路在下颌骨发育中的作用。

Low Doses of Rifampicin Used in New Tuberculosis Patients Correlated to Increased Frequency of Rifampicin-Resistance and Poorer Treatment Outcomes

The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.

Artificial simulated saliva,gastric and intestinal digestion and fermentation in vitro by human gut microbiota of intrapolysaccharide from Paecilomyces cicadae TJJ1213

In this study,the in vitro digestion and fermentation of two intra-polysaccharide fractions(IPS1 and IPS2)from Paecilomyces cicadae TJJ1213 were investigated.The constituent monosaccharides of IPS1 and IPS2 were not changed after simulated saliva,gastric and small intestinal digestion.However,they can be hydrolyzed and utilized by gut microbiota,and short-chain fatty acids(SCFAs)level were increased after IPS1 and IPS2 treatments.Furthermore,16 S r RNA sequencing analysis of fermentation samples were performed.Alpha-diversity,beta-diversity and taxonomic composition differences analysis revealed that IPS1 and IPS2 promoted the proliferation of beneficial bacteria and modulated the overall structure of gut microbiota.Taxonomic comparison analysis found that IPS1 increased the relative abundances of beneficial bacteria including Megamonas,Bifidobacterium and Lactobacillus,while IPS2 could increase the abundance of Bacteroides,Parabacteroides and Phascolarctobacterium.In addition,they can also decrease the levels of pathogenic bacteria containing Escherichia-Shigella,Klebsiella and Fusobacterium.These results indicated that IPS from Paecilomyces cicadae TJJ1213 could be used as potential candidates for new functional foods.

BZD9L1 benzimidazole analogue hampers colorectal tumor progression by impeding angiogenesis

BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.

High-energy-density metal nitrides with armchair chains

Polymeric nitrogen has attracted much attention owing to its possible application as an environmentally safe high-energy-density material.Based on a crystal structure search method accelerated by the use of machine learning and graph theory and on first-principles calculations,we predict a series of metal nitrides with chain-like polynitrogen(P_(21)-AlN_(6),P2_(1)-GaN_(6),P-1-YN_(6),and P_(4)/mnc-TiN_(8)),all of which are estimated to be energetically stable below 40.8 GPa.Phonon calculations and ab initio molecular dynamics simulations at finite temperature suggest that these nitrides are dynamically stable.We find that the nitrogen in these metal nitrides can polymerize into two types of poly-N^(2-)_(4)chains,in which theπelectrons are either extended or localized.Owing to the presence of the polymerized N4 chains,these metal nitrides can store a large amount of chemical energy,which is estimated to range from 4.50 to 2.71 kJ/g.Moreover,these compounds have high detonation pressures and detonation velocities,exceeding those of conventional explosives such as TNT and HMX.

Pressure-induced phase transitions in the ZrXY(X=Si,Ge,Sn;Y=S,Se,Te)family compounds

Pressure is an effective and clean way to modify the electronic structures of materials,cause structural phase transitions and even induce the emergence of superconductivity.Here,we predicted several new phases of the Zr XY family at high pressures using the crystal structures search method together with first-principle calculations.In particular,the Zr Ge S compound undergoes an isosymmetric phase transition from P4/nmm-I to P4/nmm-II at approximately 82 GPa.Electronic band structures show that all the high-pressure phases are metallic.Among these new structures,P4/nmm-II Zr Ge S and P4/mmm Zr Ge Se can be quenched to ambient pressure with superconducting critical temperatures of approximately 8.1 K and 8.0 K,respectively.Our study provides a way to tune the structure,electronic properties,and superconducting behavior of topological materials through pressure.

Prostate Cancer Risk Prediction and Online Calculation Based on Machine Learning Algorithm

Objective To build a prostate cancer(PCa) risk prediction model based on common clinical indicators to provide a theoretical basis for the diagnosis and treatment of PCa and to evaluate the value of artificial intelligence(AI) technology under healthcare data platforms.Methods After preprocessing of the data from Population Health Data Archive,smuothly clipped absolute deviation(SCAD) was used to select features.Random forest(RF),support vector machine(SVM),back propagation neural network(BP),and convolutional neural network(CNN) were used to predict the risk of PCa,among which BP and CNN were used on the enhanced data by SMOTE.The performances of models were compared using area under the curve(AUC) of the receiving operating characteristic curve.After the optimal model was selected,we used the Shiny to develop an online calculator for PCa risk prediction based on predictive indicators.Results Inorganic phosphorus,triglycerides,and calcium were closely related to PCa in addition to the volume of fragmented tissue and free prostate-specific antigen(PSA).Among the four models,RF had the best performance in predicting PCa(accuracy:96.80%;AUC:0.975,95% CI:0.964-0.986).Followed by BP(accuracy:85.36%;AUC:0.892,95% CI:0.849-0.934) and SVM(accuracy:82.67%;AUC:0.824,95% CI:0.805-0.844).CNN performed worse(accuracy:72.37%;AUC:0.724,95% CI:0.670-0.779).An online platform for PCa risk prediction was developed based on the RF model and the predictive indicators.Conclusions This study revealed the application value of traditional machine learning and deep learning models in disease risk prediction under healthcare data platform,proposed new ideas for PCa risk prediction in patients suspected for PCa and had undergone core needle biopsy.Besides,the online calculation may enhance the practicability of AI prediction technology and facilitate medical diagnosis.

Partially Diffusive Helium-Silica Compound under High Pressure

Helium is the second most abundant element in the universe, and together with silica, they are important components of giant planets. Exploring the reactivity and state of helium and silica under high pressure is crucial for understanding of the evolution and internal structure of giant planets. Here, using first-principles calculations and crystal structure predictions, we identify four stable phases of a helium-silica compound with seven/eight-coordinated silicon atoms at pressure of 600–4000 GPa, corresponding to the interior condition of the outer planets in the solar system. The density of He Si O2 agrees with current structure models of the planets.This helium-silica compound exhibits a superionic-like helium diffusive state under the high-pressure and hightemperature conditions along the isentropes of Saturn, a metallic fluid state in Jupiter, and a solid state in the deep interiors of Uranus and Neptune. These results show that helium may affect the erosion of the rocky core in giant planets and may help to form a diluted core region, which not only highlight the reactivity of helium under high pressure but also provide evidence helpful for building more sophisticated interior models of giant planets.

Acetylacetone effectively controlled the secondary metabolites of Microcystis aeruginosa under simulated sunlight irradiation

Inactivation of cyanobacterial cells and simultaneous control of secondary metabolites is of significant necessity for the treatment of cyanobacteria-laden water.Acetylacetone(AcAc)has been reported a specific algicide to inactivate Microcystis aeruginosa(M.aeruginosa)and an effective light activator to degrade pollutants.This study systematically investigated the photodegradation ability of AcAc under xenon(Xe)irradiation on the secondary metabolites of M.aeruginosa,mainly algal organic matter(AOM),especially toxic microcystin-LR(MC-LR).Results showed that AcAc outperformed H_(2)O_(2)in destructing the protein-like substances,humic acid-like matters,aromatic proteins and fulvic-like substances of AOM.For MC-LR(250μg/L),0.05 mmol/L AcAc attained the same degradation efficiency(87.0%)as 0.1mmol/L H_(2)O_(2).The degradation mechanism of Xe/AcAc might involve photo-induced energy/electron transfer and formation of carbon center radicals.Alkaline conditions(pH>9.0)were detrimental to the photoactivity of AcAc,corresponding to the observed degradation rate constant(k_(1)value)of MC-LR drastically decreasing to 0.0013 min^(-1)as solution pH exceeded 9.0.The PO_(4)^(3-)and HCO_(3)^(-)ions had obvious inhibition effects,whereas NO_(3)^(-)slightly improved k_(1)value from 0.0277 min^(-1)to 0.0321 min^(-1).The presence of AOM did not significantly inhibit MC-LR degradation in Xe/AcAc system.In addition,the biological toxicity of MC-LR was greatly reduced after photoreaction.These results demonstrated that AcAc was an alternative algicidal agent to effectively inactivate algal cells and simultaneously control the secondary metabolites after cell lysis.Nevertheless,the concentration and irradiation conditions should be further optimized in practical application.

Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain unclear.Here,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was disrupted.Immunohistochemistry showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm synapses.Impaired synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and density.Our results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

Spatial and temporal analysis of tuberculosis in Zhejiang Province, China, 2009-2012

Background:Tuberculosis(TB)is an infectious disease of major public health concern.The disease has demonstrated large space-time variations.This study aims to explore the space-time dynamics of TB cases in an economically and geographically dynamic province in China with specific references of TB control for policy makers.Methods:Data on all reported TB cases from 2009 to 2012 were collected from the TB program at the Zhejiang Provincial Center for Disease Control and Prevention.We employed time series and exploratory spatial data analyses,including Moran’s I,Local Getis’s G_(i)^(*),and Kulldorff’s space-time scan statistics,to identify the temporal trends and spatial patterns of TB at a county level.Results:A total of 147,941 TB cases were reported during 2009–2012 in Zhejiang.A higher proportion of TB cases were younger,male,and registered permanent residents among all TB cases notified in the province.TB cases were reported most frequently in April with small peaks in June,July,and October.This disease was spatially clustering with Moran’s I values ranged from 0.29 to 0.32(p<0.001).A most likely cluster and ten secondary clusters were identified,mainly concentrated in the southeast and west counties of the province.Conclusions:This study identified seasonal patterns and significant space-time clusters of TB cases in Zhejiang,China.Poverty,migration,and seasonal effects may play important roles in potential clusters.

Study on extraction of thiophene from model gasoline with brønsted acidic ionic liquids

Brønsted acidic ionic liquids(ILs),N-methylimidazole hydrogen sulfate([HMIm]HSO_(4))and N-methylpyrrolidone hydrogen sulfate([HNMP]HSO_(4)),are synthesized and employed as extractants to extract thiophene from model gasoline(thiophene dissolved in noctane).The effect of extraction temperature,extraction time and volume ratio of ILs to model gasoline on desulfurization rates is investigated.Then,the optimal desulfurization conditions are obtained:the ratio of ILs to model gasoline is 1∶1,extraction temperature is 50℃ for[HMIm]HSO_(4)and 60℃ for[HNMP]HSO_(4),extraction time is 60 min.Meanwhile,the desulfurization rate of[HNMP]HSO_(4)for model gasoline is 62.8%,which is higher than that of[HMIm]HSO_(4)(55.5%)under optimal conditions.The reason is discussed on the basis of the interaction energy between thiophene and ILs at the B3LYP/6-311++G(d,p)level.Furthermore,the total desulfurization rate of[HNMP]HSO_(4)and[HMIm]HSO_(4)reaches 96.4%and 94.4%,respectively,by multistage extraction.Finally,the used ILs can be reused by vacuum drying,and their desulfurization rates are not significantly decreased after recycling 7 times in single-stage desulfurization.

Fluoride removal from secondary effluent of the graphite industry using electrodialysis:Optimization with response surface methodology

Response surface methodology was utilized to model and optimize the operational variables for defluoridation using an electrodialysis process as the treatment of secondary effluent of the graphite industry. Experiments were conducted using a Box-Behnken surface statistical design in order to evaluate the effects and the interaction of the influential variables including the operational voltage, initial fluoride concentration and flow rate. The regression models for defluoridation and energy consumption responses were statistically validated using analysis of variance (ANOVA);high coefficient of determination values (R^2 = 0.9772 and R^2 = 0.9814;respectively) were obtained. The quadratic model exhibited high reproducibility and a good fit of the experimental data. The optimum values of the initial fluoride concentration, voltage and flow rate were found to be 13.9 mg/L, 13.4 V, 102.5 L/h, respectively. A fluoride removal efficiency of 99.69% was observed under optimum conditions for the treatment of the secondary effluent of the graphite industry.

Brain-wide Mapping of Mono-synaptic Afferents to Different Cell Types in the Laterodorsal Tegmentum

The laterodorsal tegmentum(LDT) is a brain structure involved in distinct behaviors including arousal,reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear.Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex(VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive(PV?) GABAergic cells received preferential projections from local LDT neurons.With regard to the different subtypes of GABAergic cells, aconsiderable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatinpositive cells than to PV?cells. Diverse inputs to the LDT on a system-wide level were revealed.

Ligand effects on arsenite removal by zero-valent iron/O2: Dissolution, corrosion, oxidation and coprecipitation

Ligands may increase the yields of reactive oxygen species(ROS)in zero-valent iron(ZVI)/O2 systems.To clarify the relationship between the properties of ligands and their effects on the oxidative removal of contaminants,five common ligands(formate,acetate,oxalate,ethylenediaminetetraacetic acid(EDTA),and phosphate)as well as acetylacetone(AA)were investigated with arsenite(As(III))as the target contaminant at three initial p H values(3.0,5.0,and 7.0).The addition of these ligands to the ZVI/O2 system resulted in quite different effects on As(III)removal.EDTA enhanced the oxidation of As(III)to arsenate(As(V))but inhibited the removal of As(V).Oxalate was the only ligand in this work that accelerated both the removal of As(III)and As(V).By analyzing the ligand effects from the four aspects:dissolution of surface iron(hydr)oxides,corrosion of ZVI,reaction with ROS,and interference with precipitation,the following properties of ligands were believed to be important:ability to provide dissociable protons,complexation ability with iron,and reactivity with ROS.The complexation ability is a double-edged sword.It could enhance the generation of ROS by reducing the reduction potential of the Fe(III)/Fe(II)redox couple,but also could inhibit the removal of arsenic by coprecipitation.The elucidated relationship between the key property parameters of ligands and their effects on the ZVI/O2 system is helpful for the rational design of effective ZVI/ligand/O2 systems.

Data-driven engineering framework with AI algorithm of Ginkgo Folium tablets manufacturing

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing.Here,an original data-driven engineering framework was proposed to tackle the challenges.Firstly,from sporadic indicators to five kinds of systematic quality characteristics,nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing.Then,from simplex to the multivariate system,the digital process capability diagnosis strategy was proposed by multivariate C_(pk)integrated Bootstrap-t.The C_(pk)of Ginkgo Folium extracts,granules,and tablets were discovered,which was 0.59,0.42,and 0.78,respectively,indicating a relatively weak process capability,especially in granulating.Furthermore,the quality traceability was discovered from unit to end-to-end analysis,which decreased from 2.17 to 1.73.This further proved that attention should be paid to granulating to improve the quality characteristic.In conclusion,this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Multichannel Financing Reduces Economic Burden and Improves the Medical Security Level for Tuberculosis Patients

Tuberculosis(TB)is one of the main infectious diseases to simultaneously cause poverty and be caused by poverty.Reducing the economic burden of TB patients in China is essential to improving patient compliance and reducing the impact of the TB epidemic.In accordance with the national reform of the medical and health system and the current status of the country’s TB prevention and treatment service system,representatives of the government proposed the concept of a multichannel financing mechanism.

Performance Comparison of Computational Methods for the Prediction of the Function and Pathogenicity of Non-coding Variants

Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects.Hence,an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences.However,it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods.To solve this issue,we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets:(1)rare germline variants from clinical relevant sequence variants(ClinVar),(2)rare somatic variants from Catalogue Of Somatic Mutations In Cancer(COSMIC),(3)common regulatory variants from curated expression quantitative trait locus(eQTL)data,and(4)disease-associated common variants from curated genomewide association studies(GWAS).All 24 tested methods performed differently under various conditions,indicating varying strengths and weaknesses under different scenarios.Importantly,the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve(AUROC)of 0.4481–0.8033 and poor for rare somatic variants from COSMIC(AUROC=0.4984–0.7131),common regulatory variants from curated eQTL data(AUROC=0.4837–0.6472),and disease-associated common variants from curated GWAS(AUROC=0.4766–0.5188).We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder,and found that the combined annotation-dependent depletion(CADD)and context-dependent tolerance score(CDTS)methods showed better performance.Summarily,we assessed the performance of 24 computational methods under diverse scenarios,providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants.